Hepatic transforming growth factor beta gives rise to tumor-initiating cells and promotes liver cancer development
Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor‐β (TGF‐β) in diethylnitro...
Saved in:
| Published in | Hepatology (Baltimore, Md.) Vol. 56; no. 6; pp. 2255 - 2267 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.12.2012
Wiley Wolters Kluwer Health, Inc |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0270-9139 1527-3350 1527-3350 |
| DOI | 10.1002/hep.26007 |
Cover
Loading…
| Abstract | Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor‐β (TGF‐β) in diethylnitrosamine (DEN)‐induced rat hepatocarcinogenesis and cirrhotic livers of HCC patients. Using several experimental approaches, including 2‐acetylaminofluorene/partial hepatectomy (2‐AAF/PHx) and 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC)‐elicited murine liver regeneration, we found that activation of LPCs in the absence of TGF‐β induction was insufficient to trigger hepatocarcinogenesis. Moreover, a small fraction of LPCs was detected to coexpress tumor initiating cell (T‐IC) markers during rat hepatocarcinogenesis and in human HCCs, and TGF‐β levels were positively correlated with T‐IC marker expression, which indicates a role of TGF‐β in T‐IC generation. Rat pluripotent LPC‐like WB‐F344 cells were exposed to low doses of TGF‐β for 18 weeks imitating the enhanced TGF‐β expression in cirrhotic liver. Interestingly, long‐term treatment of TGF‐β on WB‐F344 cells impaired their LPC potential but granted them T‐IC properties including expression of T‐IC markers, increased self‐renewal capacity, stronger chemoresistance, and tumorigenicity in NOD‐SCID mice. Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF‐β‐treated WB‐F344 cells. Introduction of the dominant‐negative mutant of Akt significantly attenuated T‐IC properties of those transformed WB‐F344 cells, indicating Akt was required in TGF‐β‐mediated‐generation of hepatic T‐ICs. We further demonstrate that TGF‐β‐induced Akt activation and LPC transformation was mediated by microRNA‐216a‐modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression. Conclusion: Hepatoma‐initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF‐β stimulation in cirrhotic liver, and pharmaceutical inhibition of microRNA‐216a/PTEN/Akt signaling could be a novel strategy for HCC prevention and therapy targeting hepatic T‐ICs. (HEPATOLOGY 2012;56:2255–2267) |
|---|---|
| AbstractList | Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor‐β (TGF‐β) in diethylnitrosamine (DEN)‐induced rat hepatocarcinogenesis and cirrhotic livers of HCC patients. Using several experimental approaches, including 2‐acetylaminofluorene/partial hepatectomy (2‐AAF/PHx) and 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC)‐elicited murine liver regeneration, we found that activation of LPCs in the absence of TGF‐β induction was insufficient to trigger hepatocarcinogenesis. Moreover, a small fraction of LPCs was detected to coexpress tumor initiating cell (T‐IC) markers during rat hepatocarcinogenesis and in human HCCs, and TGF‐β levels were positively correlated with T‐IC marker expression, which indicates a role of TGF‐β in T‐IC generation. Rat pluripotent LPC‐like WB‐F344 cells were exposed to low doses of TGF‐β for 18 weeks imitating the enhanced TGF‐β expression in cirrhotic liver. Interestingly, long‐term treatment of TGF‐β on WB‐F344 cells impaired their LPC potential but granted them T‐IC properties including expression of T‐IC markers, increased self‐renewal capacity, stronger chemoresistance, and tumorigenicity in NOD‐SCID mice. Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF‐β‐treated WB‐F344 cells. Introduction of the dominant‐negative mutant of Akt significantly attenuated T‐IC properties of those transformed WB‐F344 cells, indicating Akt was required in TGF‐β‐mediated‐generation of hepatic T‐ICs. We further demonstrate that TGF‐β‐induced Akt activation and LPC transformation was mediated by microRNA‐216a‐modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression. Conclusion: Hepatoma‐initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF‐β stimulation in cirrhotic liver, and pharmaceutical inhibition of microRNA‐216a/PTEN/Akt signaling could be a novel strategy for HCC prevention and therapy targeting hepatic T‐ICs. (HEPATOLOGY 2012;56:2255–2267) Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor-[beta] (TGF-[beta]) in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis and cirrhotic livers of HCC patients. Using several experimental approaches, including 2-acetylaminofluorene/partial hepatectomy (2-AAF/PHx) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-elicited murine liver regeneration, we found that activation of LPCs in the absence of TGF-[beta] induction was insufficient to trigger hepatocarcinogenesis. Moreover, a small fraction of LPCs was detected to coexpress tumor initiating cell (T-IC) markers during rat hepatocarcinogenesis and in human HCCs, and TGF-[beta] levels were positively correlated with T-IC marker expression, which indicates a role of TGF-[beta] in T-IC generation. Rat pluripotent LPC-like WB-F344 cells were exposed to low doses of TGF-[beta] for 18 weeks imitating the enhanced TGF-[beta] expression in cirrhotic liver. Interestingly, long-term treatment of TGF-[beta] on WB-F344 cells impaired their LPC potential but granted them T-IC properties including expression of T-IC markers, increased self-renewal capacity, stronger chemoresistance, and tumorigenicity in NOD-SCID mice. Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF-[beta]-treated WB-F344 cells. Introduction of the dominant-negative mutant of Akt significantly attenuated T-IC properties of those transformed WB-F344 cells, indicating Akt was required in TGF-[beta]-mediated-generation of hepatic T-ICs. We further demonstrate that TGF-[beta]-induced Akt activation and LPC transformation was mediated by microRNA-216a-modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression. Conclusion: Hepatoma-initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF-[beta] stimulation in cirrhotic liver, and pharmaceutical inhibition of microRNA-216a/PTEN/Akt signaling could be a novel strategy for HCC prevention and therapy targeting hepatic T-ICs. (HEPATOLOGY 2012;56:2255-2267) [PUBLICATION ABSTRACT] Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor-β (TGF-β) in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis and cirrhotic livers of HCC patients. Using several experimental approaches, including 2-acetylaminofluorene/partial hepatectomy (2-AAF/PHx) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-elicited murine liver regeneration, we found that activation of LPCs in the absence of TGF-β induction was insufficient to trigger hepatocarcinogenesis. Moreover, a small fraction of LPCs was detected to coexpress tumor initiating cell (T-IC) markers during rat hepatocarcinogenesis and in human HCCs, and TGF-β levels were positively correlated with T-IC marker expression, which indicates a role of TGF-β in T-IC generation. Rat pluripotent LPC-like WB-F344 cells were exposed to low doses of TGF-β for 18 weeks imitating the enhanced TGF-β expression in cirrhotic liver. Interestingly, long-term treatment of TGF-β on WB-F344 cells impaired their LPC potential but granted them T-IC properties including expression of T-IC markers, increased self-renewal capacity, stronger chemoresistance, and tumorigenicity in NOD-SCID mice. Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF-β-treated WB-F344 cells. Introduction of the dominant-negative mutant of Akt significantly attenuated T-IC properties of those transformed WB-F344 cells, indicating Akt was required in TGF-β-mediated-generation of hepatic T-ICs. We further demonstrate that TGF-β-induced Akt activation and LPC transformation was mediated by microRNA-216a-modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression.UNLABELLEDLiver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor-β (TGF-β) in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis and cirrhotic livers of HCC patients. Using several experimental approaches, including 2-acetylaminofluorene/partial hepatectomy (2-AAF/PHx) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-elicited murine liver regeneration, we found that activation of LPCs in the absence of TGF-β induction was insufficient to trigger hepatocarcinogenesis. Moreover, a small fraction of LPCs was detected to coexpress tumor initiating cell (T-IC) markers during rat hepatocarcinogenesis and in human HCCs, and TGF-β levels were positively correlated with T-IC marker expression, which indicates a role of TGF-β in T-IC generation. Rat pluripotent LPC-like WB-F344 cells were exposed to low doses of TGF-β for 18 weeks imitating the enhanced TGF-β expression in cirrhotic liver. Interestingly, long-term treatment of TGF-β on WB-F344 cells impaired their LPC potential but granted them T-IC properties including expression of T-IC markers, increased self-renewal capacity, stronger chemoresistance, and tumorigenicity in NOD-SCID mice. Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF-β-treated WB-F344 cells. Introduction of the dominant-negative mutant of Akt significantly attenuated T-IC properties of those transformed WB-F344 cells, indicating Akt was required in TGF-β-mediated-generation of hepatic T-ICs. We further demonstrate that TGF-β-induced Akt activation and LPC transformation was mediated by microRNA-216a-modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression.Hepatoma-initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF-β stimulation in cirrhotic liver, and pharmaceutical inhibition of microRNA-216a/PTEN/Akt signaling could be a novel strategy for HCC prevention and therapy targeting hepatic T-ICs.CONCLUSIONHepatoma-initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF-β stimulation in cirrhotic liver, and pharmaceutical inhibition of microRNA-216a/PTEN/Akt signaling could be a novel strategy for HCC prevention and therapy targeting hepatic T-ICs. Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor-β (TGF-β) in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis and cirrhotic livers of HCC patients. Using several experimental approaches, including 2-acetylaminofluorene/partial hepatectomy (2-AAF/PHx) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-elicited murine liver regeneration, we found that activation of LPCs in the absence of TGF-β induction was insufficient to trigger hepatocarcinogenesis. Moreover, a small fraction of LPCs was detected to coexpress tumor initiating cell (T-IC) markers during rat hepatocarcinogenesis and in human HCCs, and TGF-β levels were positively correlated with T-IC marker expression, which indicates a role of TGF-β in T-IC generation. Rat pluripotent LPC-like WB-F344 cells were exposed to low doses of TGF-β for 18 weeks imitating the enhanced TGF-β expression in cirrhotic liver. Interestingly, long-term treatment of TGF-β on WB-F344 cells impaired their LPC potential but granted them T-IC properties including expression of T-IC markers, increased self-renewal capacity, stronger chemoresistance, and tumorigenicity in NOD-SCID mice. Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF-β-treated WB-F344 cells. Introduction of the dominant-negative mutant of Akt significantly attenuated T-IC properties of those transformed WB-F344 cells, indicating Akt was required in TGF-β-mediated-generation of hepatic T-ICs. We further demonstrate that TGF-β-induced Akt activation and LPC transformation was mediated by microRNA-216a-modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression. Hepatoma-initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF-β stimulation in cirrhotic liver, and pharmaceutical inhibition of microRNA-216a/PTEN/Akt signaling could be a novel strategy for HCC prevention and therapy targeting hepatic T-ICs. |
| Author | Wen, Wen Xie, Wei-Fen Ning, Bei-Fang Yang, Wen Huang, Lei Wang, Hong-Yang Ding, Jin Sun, Wen Feng, Gen-Sheng Wu, Kun Wang, Chao Wu, Meng-Chao Chen, Cheng Li, Zhong Han, Tao |
| Author_xml | – sequence: 1 givenname: Kun surname: Wu fullname: Wu, Kun organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 2 givenname: Jin surname: Ding fullname: Ding, Jin organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 3 givenname: Cheng surname: Chen fullname: Chen, Cheng organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 4 givenname: Wen surname: Sun fullname: Sun, Wen organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 5 givenname: Bei-Fang surname: Ning fullname: Ning, Bei-Fang organization: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China – sequence: 6 givenname: Wen surname: Wen fullname: Wen, Wen organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 7 givenname: Lei surname: Huang fullname: Huang, Lei organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 8 givenname: Tao surname: Han fullname: Han, Tao organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 9 givenname: Wen surname: Yang fullname: Yang, Wen organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 10 givenname: Chao surname: Wang fullname: Wang, Chao organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 11 givenname: Zhong surname: Li fullname: Li, Zhong organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 12 givenname: Meng-Chao surname: Wu fullname: Wu, Meng-Chao organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 13 givenname: Gen-Sheng surname: Feng fullname: Feng, Gen-Sheng organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China – sequence: 14 givenname: Wei-Fen surname: Xie fullname: Xie, Wei-Fen organization: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China – sequence: 15 givenname: Hong-Yang surname: Wang fullname: Wang, Hong-Yang email: hywangk@vip.sina.com organization: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26853036$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22898879$$D View this record in MEDLINE/PubMed |
| BookMark | eNp1kc1uEzEUhS1URNPCghdAlhBSWUzrn_HYXqKqNEhVYQEUsbFsx5O6zNjBdvrz9nhIAlIFq7v5vqN77zkAeyEGB8BLjI4xQuTk2q2OSYcQfwJmmBHeUMrQHpghwlEjMZX74CDnG4SQbIl4BvYJEVIILmcgzd1KF29hSTrkPqbRhyVcpnhXrmGvbYkJGlc0XPpbl2Hy2cESYVmPMTU--OKrXQ3rhiFDHRZwleIYS2WHaiRodbB1LNytG-JqdKE8B097PWT3YjsPwZf3Z59P583Fx_MPp-8uGtsKXm_ohGiJJD1eaMkRMQJbIamxiPRMOmxMj3tjhRaaYy6Jlqg3RjLjmEYGtfQQHG1y60Y_1y4XNfo87amDi-usMCG0pYSxCX39CL2J6xTqdhOFWcfabqJebam1Gd1CrZIfdXpQu29W4M0W0Nnqoa8vtT7_5TrBKKJd5U42nE0x5-R6ZX2pf4yhtuAHhZGaelW1V_W712q8fWTsQv_FbtPv_OAe_g-q-dmnndFsDJ-Lu_9j6PRDdZxypq4uz9U3_v1Ktl87dUl_AW65wSg |
| CODEN | HPTLD9 |
| CitedBy_id | crossref_primary_10_1038_s41575_021_00508_3 crossref_primary_10_1002_hep_31792 crossref_primary_10_1002_mc_23298 crossref_primary_10_1155_2016_1492694 crossref_primary_10_1111_1751_2980_13072 crossref_primary_10_3390_cancers13194876 crossref_primary_10_1016_j_cellsig_2013_05_027 crossref_primary_10_1590_s0102_865020180030000002 crossref_primary_10_1002_hep_26369 crossref_primary_10_1016_j_jhep_2017_01_010 crossref_primary_10_1038_s41698_018_0048_z crossref_primary_10_1002_advs_202207349 crossref_primary_10_4137_CMO_S7633 crossref_primary_10_1016_j_toxlet_2014_08_024 crossref_primary_10_3390_ijms242417152 crossref_primary_10_1186_s12885_015_1798_4 crossref_primary_10_14348_molcells_2015_2356 crossref_primary_10_1158_0008_5472_CAN_17_2061 crossref_primary_10_1042_BCJ20210254 crossref_primary_10_1111_fcp_12297 crossref_primary_10_4252_wjsc_v6_i5_579 crossref_primary_10_1007_s43152_024_00053_6 crossref_primary_10_1007_s12272_014_0439_9 crossref_primary_10_1016_j_canlet_2017_01_037 crossref_primary_10_1007_s13765_014_4179_9 crossref_primary_10_1038_nrgastro_2013_183 crossref_primary_10_18632_oncotarget_4089 crossref_primary_10_3390_cancers16223723 crossref_primary_10_18632_oncotarget_3435 crossref_primary_10_1002_cam4_2553 crossref_primary_10_1139_cjpp_2014_0032 crossref_primary_10_3390_ijms19071939 crossref_primary_10_1155_2014_486407 crossref_primary_10_1172_JCI66024 crossref_primary_10_3390_cancers11081076 crossref_primary_10_1016_j_gene_2018_10_087 crossref_primary_10_3390_ijms17030408 crossref_primary_10_1155_2016_6304385 crossref_primary_10_1016_j_freeradbiomed_2014_04_020 crossref_primary_10_1016_j_bbcan_2014_05_001 crossref_primary_10_3390_jcm5030037 crossref_primary_10_1016_j_bbi_2016_08_016 crossref_primary_10_1158_1535_7163_MCT_14_0209 crossref_primary_10_3892_ol_2024_14669 crossref_primary_10_7314_APJCP_2014_15_1_161 crossref_primary_10_3390_jcm5010007 crossref_primary_10_3390_ijms20071723 crossref_primary_10_3390_ijms242417539 crossref_primary_10_1002_hep_29372 crossref_primary_10_1053_j_gastro_2017_11_015 crossref_primary_10_1186_s13046_019_1326_5 crossref_primary_10_1007_s12072_013_9498_0 crossref_primary_10_1038_s41419_022_04759_z crossref_primary_10_1007_s13346_024_01780_x crossref_primary_10_1007_s13277_015_3920_2 crossref_primary_10_1016_j_jhep_2015_03_036 crossref_primary_10_1038_nrgastro_2014_6 crossref_primary_10_3390_cancers12102746 crossref_primary_10_1002_jcb_29496 crossref_primary_10_1016_j_dld_2019_07_014 crossref_primary_10_1016_j_neo_2014_07_005 crossref_primary_10_1038_onc_2016_89 crossref_primary_10_1158_0008_5472_CAN_14_0243 crossref_primary_10_1002_ar_23357 crossref_primary_10_1002_hep4_1145 crossref_primary_10_18632_oncotarget_15304 crossref_primary_10_1016_j_bbrc_2014_10_023 crossref_primary_10_1155_2019_8734362 crossref_primary_10_1007_s11684_013_0256_4 crossref_primary_10_1016_j_biopha_2017_12_035 crossref_primary_10_1016_j_gene_2018_10_051 crossref_primary_10_1111_fcp_12990 crossref_primary_10_1038_s41388_022_02246_5 crossref_primary_10_1080_15384101_2021_1874694 crossref_primary_10_1007_s12035_014_8867_6 crossref_primary_10_1186_1471_2121_15_5 crossref_primary_10_1016_j_canlet_2015_07_018 crossref_primary_10_1371_journal_pone_0079409 crossref_primary_10_1002_adtp_202000025 crossref_primary_10_1016_j_ijpharm_2022_121622 crossref_primary_10_1177_1535370215584935 crossref_primary_10_1016_j_canlet_2013_12_024 crossref_primary_10_1016_j_tox_2013_02_001 crossref_primary_10_1038_s41392_024_01851_y crossref_primary_10_1002_jcp_24488 crossref_primary_10_3390_cancers10060183 crossref_primary_10_1177_1010428319834856 crossref_primary_10_1016_j_cellsig_2013_03_022 crossref_primary_10_1371_journal_pone_0144433 crossref_primary_10_1186_s40164_021_00212_7 crossref_primary_10_3390_molecules25122883 crossref_primary_10_1016_j_dld_2016_06_001 crossref_primary_10_1158_1535_7163_MCT_13_0099 crossref_primary_10_1053_j_gastro_2013_01_056 crossref_primary_10_3390_ijms17010030 crossref_primary_10_1186_s12935_015_0253_6 crossref_primary_10_1007_s11427_018_9365_7 crossref_primary_10_1016_j_canlet_2018_01_001 crossref_primary_10_1186_s12943_016_0572_9 crossref_primary_10_1002_hep_26323 crossref_primary_10_1038_oncsis_2016_6 crossref_primary_10_1111_liv_13377 crossref_primary_10_15406_mojcsr_2014_01_00012 crossref_primary_10_1002_adtp_202400126 crossref_primary_10_1016_j_canlet_2016_03_014 crossref_primary_10_1155_2013_924206 crossref_primary_10_3892_ol_2018_8672 crossref_primary_10_1016_S1499_3872_13_60104_6 crossref_primary_10_1007_s12015_023_10639_6 crossref_primary_10_1038_oncsis_2017_81 crossref_primary_10_1177_1010428317695923 crossref_primary_10_1016_j_omtn_2019_12_043 crossref_primary_10_1245_s10434_015_5035_9 crossref_primary_10_1016_j_semcancer_2017_11_007 crossref_primary_10_1586_17474124_2013_846826 crossref_primary_10_1016_j_biochi_2018_03_003 crossref_primary_10_1016_j_trecan_2022_10_005 crossref_primary_10_1186_s43556_024_00184_0 crossref_primary_10_1007_s11356_021_15571_1 crossref_primary_10_18632_oncotarget_12569 crossref_primary_10_1016_j_canlet_2015_07_041 crossref_primary_10_1039_C6MD00391E crossref_primary_10_3389_fonc_2018_00357 crossref_primary_10_1002_cbin_10341 crossref_primary_10_1111_hepr_12747 crossref_primary_10_1016_j_yexcr_2019_111781 crossref_primary_10_1002_stem_3038 crossref_primary_10_1016_j_critrevonc_2016_08_006 crossref_primary_10_1016_j_msec_2020_111446 crossref_primary_10_1089_jir_2017_0130 crossref_primary_10_1371_journal_pone_0080789 crossref_primary_10_2131_jts_39_837 crossref_primary_10_1002_mc_22906 crossref_primary_10_3390_cancers12030684 crossref_primary_10_1016_j_neo_2014_08_010 crossref_primary_10_1111_acer_12279 crossref_primary_10_18632_aging_205725 crossref_primary_10_1038_s41388_019_1107_9 crossref_primary_10_1002_hep_28919 crossref_primary_10_1016_j_canlet_2016_03_033 crossref_primary_10_1016_j_bbcan_2023_188870 crossref_primary_10_1016_j_fob_2015_05_009 crossref_primary_10_1016_j_jinorgbio_2023_112200 crossref_primary_10_1002_mc_22592 crossref_primary_10_4254_wjh_v13_i3_328 crossref_primary_10_1016_j_jep_2018_11_007 crossref_primary_10_1016_j_ebiom_2019_01_058 crossref_primary_10_3389_fonc_2023_1073859 crossref_primary_10_3390_cancers11111652 crossref_primary_10_1016_j_abb_2015_11_004 crossref_primary_10_3748_wjg_v20_i30_10249 crossref_primary_10_1186_s12967_023_04425_8 crossref_primary_10_1002_jcp_24962 crossref_primary_10_1111_hepr_12606 crossref_primary_10_3389_fimmu_2020_00140 crossref_primary_10_1016_j_cellimm_2017_08_004 crossref_primary_10_1371_journal_pone_0096698 crossref_primary_10_3390_cancers11030345 crossref_primary_10_1038_onc_2014_258 crossref_primary_10_1002_hep_30166 crossref_primary_10_1007_s11684_023_1049_z |
| Cites_doi | 10.1053/j.gastro.2007.06.016 10.1053/jhep.2002.32089 10.1038/nrc1232 10.1159/000218340 10.1053/jhep.2001.28457 10.1002/hep.22704 10.1016/j.canlet.2005.11.042 10.1016/j.ccr.2007.05.008 10.1016/j.ccr.2008.01.013 10.1172/JCI24282 10.1038/nm1377 10.1038/ncb1897 10.1002/hep.22283 10.1002/hep.21466 10.1002/hep.24530 10.1053/j.gastro.2004.09.014 10.1016/S1535-6108(04)00058-3 10.1083/jcb.200305112 10.1002/hep.21227 10.3181/00379727-204-43663 10.1016/j.stem.2011.06.005 10.3322/caac.20107 10.1016/j.cell.2008.07.001 10.1002/hep.23449 10.1038/nature08734 10.1182/blood-2009-11-255778 10.1073/pnas.0705395105 10.1038/nature04703 10.1073/pnas.111614398 10.1038/sj.onc.1210811 10.1038/sj.onc.1208475 10.1634/stemcells.2005-0108 10.1016/j.cell.2006.12.029 10.1002/hep.22580 10.1002/ajmg.a.10750 10.1016/0014-4827(84)90666-9 10.1038/nature07086 10.1016/j.stem.2007.02.001 10.1016/j.cell.2007.10.054 10.1074/jbc.R800071200 10.1038/ng1494 10.1038/nature05529 10.1016/S0140-6736(08)60383-9 10.1073/pnas.0810956106 10.1002/hep.24675 10.1158/0008-5472.CAN-07-6691 10.1002/hep.1840160604 10.1038/emm.2001.31 10.1002/hep.23544 10.1053/j.gastro.2007.05.022 10.1016/j.jhep.2010.05.003 10.1002/hep.510300614 10.1136/gut.2005.088690 10.1016/S0092-8674(04)00045-5 10.1002/hep.23793 |
| ContentType | Journal Article |
| Copyright | Copyright © 2012 American Association for the Study of Liver Diseases 2014 INIST-CNRS Copyright © 2012 American Association for the Study of Liver Diseases. |
| Copyright_xml | – notice: Copyright © 2012 American Association for the Study of Liver Diseases – notice: 2014 INIST-CNRS – notice: Copyright © 2012 American Association for the Study of Liver Diseases. |
| DBID | BSCLL AAYXX CITATION IQODW CGR CUY CVF ECM EIF NPM 7T5 7TM 7TO 7U9 H94 K9. 7X8 |
| DOI | 10.1002/hep.26007 |
| DatabaseName | Istex CrossRef Pascal-Francis Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Immunology Abstracts Nucleic Acids Abstracts Oncogenes and Growth Factors Abstracts Virology and AIDS Abstracts AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Immunology Abstracts Virology and AIDS Abstracts Oncogenes and Growth Factors Abstracts Nucleic Acids Abstracts MEDLINE - Academic |
| DatabaseTitleList | AIDS and Cancer Research Abstracts MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1527-3350 |
| EndPage | 2267 |
| ExternalDocumentID | 2831418311 22898879 26853036 10_1002_hep_26007 HEP26007 ark_67375_WNG_X7ZW94V6_N |
| Genre | article Research Support, Non-U.S. Gov't Journal Article |
| GrantInformation_xml | – fundername: Ministry of Science and Technology Key Program funderid: 2012ZX10002‐009; 011; 013 – fundername: National Natural Science Foundation of China funderid: 30921006; 31071236 |
| GroupedDBID | --- --K .3N .55 .GA .GJ .Y3 05W 0R~ 10A 186 1B1 1CY 1L6 1OB 1OC 1ZS 1~5 24P 31~ 33P 3O- 3SF 3WU 4.4 4G. 4ZD 50Y 50Z 51W 51X 52M 52N 52O 52P 52R 52S 52T 52U 52V 52W 52X 53G 5GY 5RE 5VS 7-5 702 7PT 8-0 8-1 8-3 8-4 8-5 8UM 930 A01 A03 AAEDT AAESR AAEVG AAHHS AALRI AAONW AAQFI AAQQT AAQXK AASGY AAXRX AAXUO AAZKR ABCQN ABCUV ABEML ABIJN ABLJU ABMAC ABOCM ABPVW ABXGK ACAHQ ACBWZ ACCFJ ACCZN ACGFS ACMXC ACPOU ACPRK ACSCC ACXBN ACXQS ADBBV ADEOM ADIZJ ADKYN ADMGS ADMUD ADOZA ADXAS ADZMN ADZOD AECAP AEEZP AEIMD AENEX AEQDE AEUQT AFBPY AFFNX AFGKR AFPWT AFUWQ AFZJQ AHMBA AIACR AIURR AIWBW AJAOE AJBDE ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMYDB ASPBG ATUGU AVWKF AZBYB AZFZN AZVAB BAFTC BAWUL BDRZF BHBCM BMXJE BROTX BRXPI BSCLL BY8 C45 CAG COF CS3 D-6 D-7 D-E D-F DCZOG DIK DPXWK DR2 DRFUL DRMAN DRSTM DU5 E3Z EBS EJD F00 F01 F04 F5P FD8 FDB FEDTE FGOYB FUBAC G-S G.N GNP GODZA H.X HBH HF~ HHY HHZ HVGLF HZ~ IHE IX1 J0M J5H JPC KBYEO KQQ LATKE LC2 LC3 LEEKS LH4 LITHE LOXES LP6 LP7 LUTES LW6 LYRES M41 M65 MJL MK4 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM N04 N05 N4W N9A NF~ NNB NQ- O66 O9- OIG OK1 OVD P2P P2W P2X P2Z P4B P4D PALCI PQQKQ Q.N Q11 QB0 QRW R.K R2- RGB RIG RIWAO RJQFR ROL RPZ RWI RX1 RYL SEW SSZ SUPJJ TEORI UB1 V2E V9Y W2D W8V W99 WBKPD WH7 WHWMO WIB WIH WIJ WIK WIN WJL WOHZO WQJ WRC WUP WVDHM WXI X7M XG1 XV2 ZGI ZXP ZZTAW ~IA ~WT AANHP ABWVN ACLDA ACRPL ACYXJ ADNMO AAYXX ABJNI ACZKN AFNMH AGQPQ AHQVU CITATION MEWTI WXSBR ACIJW IQODW AAMMB AEFGJ AGXDD AIDQK AIDYY CGR CUY CVF ECM EIF NPM 7T5 7TM 7TO 7U9 H94 K9. 7X8 |
| ID | FETCH-LOGICAL-c4877-36884292f1da9702b81c893bc02f59e1bbf1fbc8a8a71792a90fbb95be5a0b043 |
| IEDL.DBID | DR2 |
| ISSN | 0270-9139 1527-3350 |
| IngestDate | Fri Jul 11 08:57:49 EDT 2025 Fri Jul 25 22:58:29 EDT 2025 Mon Jul 21 05:43:48 EDT 2025 Wed Apr 02 07:49:42 EDT 2025 Tue Jul 01 03:33:33 EDT 2025 Thu Apr 24 23:02:13 EDT 2025 Wed Jan 22 16:21:01 EST 2025 Wed Oct 30 09:59:44 EDT 2024 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6 |
| Keywords | Liver cancer Transforming growth factor Liver Gastroenterology Digestive diseases Hepatic disease Malignant tumor Tumor cell Cancer |
| Language | English |
| License | http://doi.wiley.com/10.1002/tdm_license_1.1 CC BY 4.0 Copyright © 2012 American Association for the Study of Liver Diseases. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c4877-36884292f1da9702b81c893bc02f59e1bbf1fbc8a8a71792a90fbb95be5a0b043 |
| Notes | Ministry of Science and Technology Key Program - No. 2012ZX10002-009; No. 011; No. 013 Potential conflict of interest: Nothing to report. Supported in part by grants from National Natural Science Foundation of China 30921006 and 31071236; Ministry of Science and Technology Key Program 2012ZX10002-009, 011, and 013; Shanghai Pujiang Program. istex:EEBEE56350E618C8B60E5B3E2B20F4F45E535E35 ark:/67375/WNG-X7ZW94V6-N ArticleID:HEP26007 National Natural Science Foundation of China - No. 30921006; No. 31071236 These authors contributed equally to this work. Supported in part by grants from National Natural Science Foundation of China 30921006 and 31071236; Ministry of Science and Technology Key Program 2012ZX10002‐009, 011, and 013; Shanghai Pujiang Program. fax: 86‐21‐65566851 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 |
| PMID | 22898879 |
| PQID | 1221565464 |
| PQPubID | 996352 |
| PageCount | 13 |
| ParticipantIDs | proquest_miscellaneous_1223432554 proquest_journals_1221565464 pubmed_primary_22898879 pascalfrancis_primary_26853036 crossref_citationtrail_10_1002_hep_26007 crossref_primary_10_1002_hep_26007 wiley_primary_10_1002_hep_26007_HEP26007 istex_primary_ark_67375_WNG_X7ZW94V6_N |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | December 2012 |
| PublicationDateYYYYMMDD | 2012-12-01 |
| PublicationDate_xml | – month: 12 year: 2012 text: December 2012 |
| PublicationDecade | 2010 |
| PublicationPlace | Hoboken |
| PublicationPlace_xml | – name: Hoboken – name: Hoboken, NJ – name: United States |
| PublicationTitle | Hepatology (Baltimore, Md.) |
| PublicationTitleAlternate | Hepatology |
| PublicationYear | 2012 |
| Publisher | Wiley Subscription Services, Inc., A Wiley Company Wiley Wolters Kluwer Health, Inc |
| Publisher_xml | – name: Wiley Subscription Services, Inc., A Wiley Company – name: Wiley – name: Wolters Kluwer Health, Inc |
| References | Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I, et al. TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol 2009; 11: 881-889. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 2007; 131: 1109-1123. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004; 127: S35-S50. You H, Ding W, Rountree CB. Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-beta. HEPATOLOGY 2010; 51: 1635-1644. Im YH, Kim HT, Kim IY, Factor VM, Hahm KB, Anzano M, et al. Heterozygous mice for the transforming growth factor-beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis. Cancer Res 2001; 61: 6665-6668. Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 2007; 1: 101-112. Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, Onodera M, et al. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology 2007; 133: 937-950. Bissell DM, Roulot D, George J. Transforming growth factor beta and the liver. HEPATOLOGY 2001; 34: 859-867. Paik JH, Kollipara R, Chu G, Ji H, Xiao Y, Ding Z, et al. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 2007; 128: 309-323. Cohen MM Jr. TGF beta/Smad signaling system and its pathologic correlates. Am J Med Genet A 2003; 116A: 1-A10. Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, Garcia-Echeverria C, et al. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci U S A 2009; 106: 268-273. Mishra L, Banker T, Murray J, Byers S, Thenappan A, He AR, et al. Liver stem cells and hepatocellular carcinoma. HEPATOLOGY 2009; 49: 318-329. Davis BN, Hilyard AC, Lagna G, Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature 2008; 454: 56-61. Fu CT, Zhu KY, Mi JQ, Liu YF, Murray ST, Fu YF, et al. An evolutionarily conserved PTEN-C/EBPalpha-CTNNA1 axis controls myeloid development and transformation. Blood 2010; 115: 4715-4724. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-297. Lee TK, Castilho A, Cheung VC, Tang KH, Ma S, Ng IO. CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell 2011; 9: 50-63. Coulouarn C, Factor VM, Thorgeirsson SS. Transforming growth factor-beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer. HEPATOLOGY 2008; 47: 2059-2067. Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, et al. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res 2008; 68: 4287-4295. Grisham JW, Coleman WB, Smith GJ. Isolation, culture, and transplantation of rat hepatocytic precursor (stem-like) cells. Proc Soc Exp Biol Med 1993; 204: 270-279. Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. HEPATOLOGY 2008; 48: 2047-2063. Wang C, Yang W, Yan HX, Luo T, Zhang J, Tang L, et al. Hepatitis B Virus S (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine treated HBx transgenic mice. HEPATOLOGY 2012; 55: 108-120. Hill R, Wu H. PTEN, stem cells, and cancer stem cells. J Biol Chem 2009; 284: 11755-11759. Bissell DM. Chronic liver injury, TGF-beta, and cancer. Exp Mol Med 2001; 33: 179-190. Inoki K, Corradetti MN, Guan KL. Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet 2005; 37: 19-24. Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003; 3: 895-902. Naka K, Hoshii T, Muraguchi T, Tadokoro Y, Ooshio T, Kondo Y, et al. TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature 2010; 463: 676-680. Dooley S, Weng H, Mertens PR. Hypotheses on the role of transforming growth factor-beta in the onset and progression of hepatocellular carcinoma. Dig Dis 2009; 27: 93-101. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008; 27: 1749-1758. Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445: 656-660. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008; 371: 838-851. Theise ND, Saxena R, Portmann BC, Thung SN, Yee H, Chiriboga L, et al. The canals of Hering and hepatic stem cells in humans. HEPATOLOGY 1999; 30: 1425-1433. Inagaki Y, Okazaki I. Emerging insights into Transforming growth factor beta Smad signal in hepatic fibrogenesis. Gut 2007; 56: 284-292. Massagué J. TGF-β in cancer. Cell 2008; 134: 215-230. Zavadil J, Bitzer M, Liang D, Yang YC, Massimi A, Kneitz S, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci U S A 2001; 98: 6686-6691. Sun W, Ding J, Wu K, Ning BF, Wen W, Sun HY, et al. Gankyrin-mediated dedifferentiation facilitates the tumorigenicity of hepatocytes and hepatoma cells. HEPATOLOGY 2011; 54: 1259-1272. Tsao MS, Smith JD, Nelson KG, Grisham JW. A diploid epithelial cell line from normal adult rat liver with phenotypic properties of 'oval' cells. Exp Cell Res 1984; 154: 38-52. Romero-Gallo J, Sozmen EG, Chytil A, Russell WE, Whitehead R, Parks WT, et al. Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy. Oncogene 2005; 24: 3028-3041. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 2008; 13: 153-166. Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 2006; 441: 475-482. Li WL, Su J, Yao YC, Tao XR, Yan YB, Yu HY, et al. Isolation and characterization of bipotent liver progenitor cells from adult mouse. Stem Cells 2006; 24: 322-332. Tang Y, Kitisin K, Jogunoori W, Li C, Deng CX, Mueller SC, et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci U S A 2008; 105: 2445-2450. Nguyen LN, Furuya MH, Wolfraim LA, Nguyen AP, Holdren MS, Campbell JS, et al. Transforming growth factor-beta differentially regulates oval cell and hepatocyte proliferation. HEPATOLOGY 2007; 45: 31-41. Bruix J, Boix L, Sala M, Llovet JM. Focus on hepatocellular carcinoma. Cancer Cell 2004; 5: 215-219. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90. Blokzijl A, Dahlqvist C, Reissmann E, Falk A, Moliner A, Lendahl U, et al. Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3. J Cell Biol 2003; 163: 723-728. Thenappan A, Li Y, Kitisin K, Rashid A, Shetty K, Johnson L, et al. Role of transforming growth factor beta signaling and expansion of progenitor cells in regenerating liver. HEPATOLOGY 2010; 51: 1373-1382. Chiba T, Seki A, Aoki R, Ichikawa H, Negishi M, Miyagi S, et al. Bmi1 promotes hepatic stem cell expansion and tumorigenicity in both Ink4a/Arf-dependent and -independent manners in mice. HEPATOLOGY 2010; 52: 1111-1123. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007; 133: 647-658. Hsia CC, Evarts RP, Nakatsukasa H, Marsden ER, Thorgeirsson SS. Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis. HEPATOLOGY 1992; 16: 1327-1333. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115: 209-218. Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. HEPATOLOGY 2006; 44: 240-251. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007; 12: 9-22. Chow LM, Baker SJ. PTEN function in normal and neoplastic growth. Cancer Lett 2006; 241: 184-196. Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 2006; 12: 410-416. Marquardt JU, Factor VM, Thorgeirsson SS. Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications. J Hepatol 2010; 53: 568-577. Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. HEPATOLOGY 2002; 35: 519-524. 2010; 53 2004; 127 2011; 61 2010; 463 2004; 5 2011; 54 2008; 105 1992; 16 1993; 204 2012; 55 2009; 49 2005; 24 2009; 11 2001; 61 1984; 154 2006; 24 2007; 133 2010; 115 2008; 27 2007; 131 2003; 3 2008; 68 2006; 241 2009; 284 2005; 37 2007; 1 2006; 441 2001; 98 2003; 163 2007; 445 2007; 128 2006; 12 2002; 35 2005; 115 2008; 13 2007; 56 2007; 12 2009; 27 2011; 9 2004; 116 2006; 44 2008; 47 2008; 48 1999; 30 2008; 454 2001; 33 2008; 134 2001; 34 2003; 116A 2007; 45 2010; 52 2008; 371 2010; 51 2009; 106 Li (10.1002/hep.26007-BIB21|cit21) 2006; 24 Bartel (10.1002/hep.26007-BIB54|cit54) 2004; 116 Davis (10.1002/hep.26007-BIB56|cit56) 2008; 454 Meng (10.1002/hep.26007-BIB30|cit30) 2007; 133 Tsao (10.1002/hep.26007-BIB20|cit20) 1984; 154 Zavadil (10.1002/hep.26007-BIB16|cit16) 2001; 98 Hsia (10.1002/hep.26007-BIB7|cit7) 1992; 16 Yang (10.1002/hep.26007-BIB18|cit18) 2008; 68 Romero-Gallo (10.1002/hep.26007-BIB41|cit41) 2005; 24 Yang (10.1002/hep.26007-BIB37|cit37) 2008; 13 Yu (10.1002/hep.26007-BIB55|cit55) 2007; 131 Hill (10.1002/hep.26007-BIB51|cit51) 2009; 284 Guertin (10.1002/hep.26007-BIB29|cit29) 2007; 12 Chow (10.1002/hep.26007-BIB50|cit50) 2006; 241 Wang (10.1002/hep.26007-BIB11|cit11) 2012; 55 Nguyen (10.1002/hep.26007-BIB45|cit45) 2007; 45 Bataller (10.1002/hep.26007-BIB32|cit32) 2005; 115 Fu (10.1002/hep.26007-BIB52|cit52) 2010; 115 Tang (10.1002/hep.26007-BIB43|cit43) 2008; 105 Jemal (10.1002/hep.26007-BIB1|cit1) 2011; 61 Miyamoto (10.1002/hep.26007-BIB48|cit48) 2007; 1 Schuppan (10.1002/hep.26007-BIB4|cit4) 2008; 371 Cohen (10.1002/hep.26007-BIB13|cit13) 2003; 116A Sun (10.1002/hep.26007-BIB22|cit22) 2011; 54 Lee (10.1002/hep.26007-BIB25|cit25) 2011; 9 Ma (10.1002/hep.26007-BIB26|cit26) 2008; 27 Blokzijl (10.1002/hep.26007-BIB24|cit24) 2003; 163 Theise (10.1002/hep.26007-BIB6|cit6) 1999; 30 Lee (10.1002/hep.26007-BIB8|cit8) 2006; 12 Fattovich (10.1002/hep.26007-BIB5|cit5) 2004; 127 Pardal (10.1002/hep.26007-BIB46|cit46) 2003; 3 Bruix (10.1002/hep.26007-BIB3|cit3) 2004; 5 Im (10.1002/hep.26007-BIB42|cit42) 2001; 61 Chiba (10.1002/hep.26007-BIB10|cit10) 2007; 133 Dubrovska (10.1002/hep.26007-BIB49|cit49) 2009; 106 Paik (10.1002/hep.26007-BIB47|cit47) 2007; 128 Kato (10.1002/hep.26007-BIB31|cit31) 2009; 11 Xue (10.1002/hep.26007-BIB36|cit36) 2007; 445 Naka (10.1002/hep.26007-BIB28|cit28) 2010; 463 Massagué (10.1002/hep.26007-BIB15|cit15) 2008; 134 Mishra (10.1002/hep.26007-BIB34|cit34) 2009; 49 Inoki (10.1002/hep.26007-BIB27|cit27) 2005; 37 Yilmaz (10.1002/hep.26007-BIB53|cit53) 2006; 441 Bissell (10.1002/hep.26007-BIB14|cit14) 2001; 33 Chiba (10.1002/hep.26007-BIB9|cit9) 2010; 52 Inagaki (10.1002/hep.26007-BIB12|cit12) 2007; 56 Bruix (10.1002/hep.26007-BIB2|cit2) 2002; 35 Bissell (10.1002/hep.26007-BIB17|cit17) 2001; 34 Coulouarn (10.1002/hep.26007-BIB23|cit23) 2008; 47 Marquardt (10.1002/hep.26007-BIB33|cit33) 2010; 53 Thenappan (10.1002/hep.26007-BIB44|cit44) 2010; 51 Grisham (10.1002/hep.26007-BIB19|cit19) 1993; 204 Chiba (10.1002/hep.26007-BIB38|cit38) 2006; 44 You (10.1002/hep.26007-BIB39|cit39) 2010; 51 Dooley (10.1002/hep.26007-BIB40|cit40) 2009; 27 Aravalli (10.1002/hep.26007-BIB35|cit35) 2008; 48 |
| References_xml | – reference: Massagué J. TGF-β in cancer. Cell 2008; 134: 215-230. – reference: Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 2008; 13: 153-166. – reference: Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007; 133: 647-658. – reference: Nguyen LN, Furuya MH, Wolfraim LA, Nguyen AP, Holdren MS, Campbell JS, et al. Transforming growth factor-beta differentially regulates oval cell and hepatocyte proliferation. HEPATOLOGY 2007; 45: 31-41. – reference: Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004; 127: S35-S50. – reference: Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008; 27: 1749-1758. – reference: Zavadil J, Bitzer M, Liang D, Yang YC, Massimi A, Kneitz S, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci U S A 2001; 98: 6686-6691. – reference: Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, et al. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res 2008; 68: 4287-4295. – reference: Inagaki Y, Okazaki I. Emerging insights into Transforming growth factor beta Smad signal in hepatic fibrogenesis. Gut 2007; 56: 284-292. – reference: Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 2006; 441: 475-482. – reference: Sun W, Ding J, Wu K, Ning BF, Wen W, Sun HY, et al. Gankyrin-mediated dedifferentiation facilitates the tumorigenicity of hepatocytes and hepatoma cells. HEPATOLOGY 2011; 54: 1259-1272. – reference: Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. HEPATOLOGY 2008; 48: 2047-2063. – reference: Paik JH, Kollipara R, Chu G, Ji H, Xiao Y, Ding Z, et al. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 2007; 128: 309-323. – reference: Hill R, Wu H. PTEN, stem cells, and cancer stem cells. J Biol Chem 2009; 284: 11755-11759. – reference: Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, Onodera M, et al. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology 2007; 133: 937-950. – reference: Wang C, Yang W, Yan HX, Luo T, Zhang J, Tang L, et al. Hepatitis B Virus S (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine treated HBx transgenic mice. HEPATOLOGY 2012; 55: 108-120. – reference: Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. HEPATOLOGY 2006; 44: 240-251. – reference: Li WL, Su J, Yao YC, Tao XR, Yan YB, Yu HY, et al. Isolation and characterization of bipotent liver progenitor cells from adult mouse. Stem Cells 2006; 24: 322-332. – reference: Theise ND, Saxena R, Portmann BC, Thung SN, Yee H, Chiriboga L, et al. The canals of Hering and hepatic stem cells in humans. HEPATOLOGY 1999; 30: 1425-1433. – reference: Cohen MM Jr. TGF beta/Smad signaling system and its pathologic correlates. Am J Med Genet A 2003; 116A: 1-A10. – reference: Grisham JW, Coleman WB, Smith GJ. Isolation, culture, and transplantation of rat hepatocytic precursor (stem-like) cells. Proc Soc Exp Biol Med 1993; 204: 270-279. – reference: Blokzijl A, Dahlqvist C, Reissmann E, Falk A, Moliner A, Lendahl U, et al. Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3. J Cell Biol 2003; 163: 723-728. – reference: Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003; 3: 895-902. – reference: Bruix J, Boix L, Sala M, Llovet JM. Focus on hepatocellular carcinoma. Cancer Cell 2004; 5: 215-219. – reference: Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 2007; 131: 1109-1123. – reference: Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 2007; 1: 101-112. – reference: Thenappan A, Li Y, Kitisin K, Rashid A, Shetty K, Johnson L, et al. Role of transforming growth factor beta signaling and expansion of progenitor cells in regenerating liver. HEPATOLOGY 2010; 51: 1373-1382. – reference: Coulouarn C, Factor VM, Thorgeirsson SS. Transforming growth factor-beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer. HEPATOLOGY 2008; 47: 2059-2067. – reference: Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445: 656-660. – reference: Im YH, Kim HT, Kim IY, Factor VM, Hahm KB, Anzano M, et al. Heterozygous mice for the transforming growth factor-beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis. Cancer Res 2001; 61: 6665-6668. – reference: You H, Ding W, Rountree CB. Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-beta. HEPATOLOGY 2010; 51: 1635-1644. – reference: Chiba T, Seki A, Aoki R, Ichikawa H, Negishi M, Miyagi S, et al. Bmi1 promotes hepatic stem cell expansion and tumorigenicity in both Ink4a/Arf-dependent and -independent manners in mice. HEPATOLOGY 2010; 52: 1111-1123. – reference: Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 2006; 12: 410-416. – reference: Marquardt JU, Factor VM, Thorgeirsson SS. Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications. J Hepatol 2010; 53: 568-577. – reference: Lee TK, Castilho A, Cheung VC, Tang KH, Ma S, Ng IO. CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell 2011; 9: 50-63. – reference: Inoki K, Corradetti MN, Guan KL. Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet 2005; 37: 19-24. – reference: Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007; 12: 9-22. – reference: Bissell DM. Chronic liver injury, TGF-beta, and cancer. Exp Mol Med 2001; 33: 179-190. – reference: Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008; 371: 838-851. – reference: Bissell DM, Roulot D, George J. Transforming growth factor beta and the liver. HEPATOLOGY 2001; 34: 859-867. – reference: Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, Garcia-Echeverria C, et al. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci U S A 2009; 106: 268-273. – reference: Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-297. – reference: Tsao MS, Smith JD, Nelson KG, Grisham JW. A diploid epithelial cell line from normal adult rat liver with phenotypic properties of 'oval' cells. Exp Cell Res 1984; 154: 38-52. – reference: Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90. – reference: Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. HEPATOLOGY 2002; 35: 519-524. – reference: Romero-Gallo J, Sozmen EG, Chytil A, Russell WE, Whitehead R, Parks WT, et al. Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy. Oncogene 2005; 24: 3028-3041. – reference: Tang Y, Kitisin K, Jogunoori W, Li C, Deng CX, Mueller SC, et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci U S A 2008; 105: 2445-2450. – reference: Mishra L, Banker T, Murray J, Byers S, Thenappan A, He AR, et al. Liver stem cells and hepatocellular carcinoma. HEPATOLOGY 2009; 49: 318-329. – reference: Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115: 209-218. – reference: Davis BN, Hilyard AC, Lagna G, Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature 2008; 454: 56-61. – reference: Fu CT, Zhu KY, Mi JQ, Liu YF, Murray ST, Fu YF, et al. An evolutionarily conserved PTEN-C/EBPalpha-CTNNA1 axis controls myeloid development and transformation. Blood 2010; 115: 4715-4724. – reference: Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I, et al. TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol 2009; 11: 881-889. – reference: Chow LM, Baker SJ. PTEN function in normal and neoplastic growth. Cancer Lett 2006; 241: 184-196. – reference: Hsia CC, Evarts RP, Nakatsukasa H, Marsden ER, Thorgeirsson SS. Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis. HEPATOLOGY 1992; 16: 1327-1333. – reference: Dooley S, Weng H, Mertens PR. Hypotheses on the role of transforming growth factor-beta in the onset and progression of hepatocellular carcinoma. Dig Dis 2009; 27: 93-101. – reference: Naka K, Hoshii T, Muraguchi T, Tadokoro Y, Ooshio T, Kondo Y, et al. TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature 2010; 463: 676-680. – volume: 27 start-page: 1749 year: 2008 end-page: 1758 article-title: CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway publication-title: Oncogene – volume: 35 start-page: 519 year: 2002 end-page: 524 article-title: Prognostic prediction and treatment strategy in hepatocellular carcinoma publication-title: HEPATOLOGY – volume: 1 start-page: 101 year: 2007 end-page: 112 article-title: Foxo3a is essential for maintenance of the hematopoietic stem cell pool publication-title: Cell Stem Cell – volume: 115 start-page: 209 year: 2005 end-page: 218 article-title: Liver fibrosis publication-title: J Clin Invest – volume: 3 start-page: 895 year: 2003 end-page: 902 article-title: Applying the principles of stem‐cell biology to cancer publication-title: Nat Rev Cancer – volume: 133 start-page: 937 year: 2007 end-page: 950 article-title: Enhanced self‐renewal capability in hepatic stem/progenitor cells drives cancer initiation publication-title: Gastroenterology – volume: 5 start-page: 215 year: 2004 end-page: 219 article-title: Focus on hepatocellular carcinoma publication-title: Cancer Cell – volume: 12 start-page: 410 year: 2006 end-page: 416 article-title: A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells publication-title: Nat Med – volume: 11 start-page: 881 year: 2009 end-page: 889 article-title: TGF‐beta activates Akt kinase through a microRNA‐dependent amplifying circuit targeting PTEN publication-title: Nat Cell Biol – volume: 116 start-page: 281 year: 2004 end-page: 297 article-title: MicroRNAs: genomics, biogenesis, mechanism, and function publication-title: Cell – volume: 128 start-page: 309 year: 2007 end-page: 323 article-title: FoxOs are lineage‐restricted redundant tumor suppressors and regulate endothelial cell homeostasis publication-title: Cell – volume: 61 start-page: 69 year: 2011 end-page: 90 article-title: Global cancer statistics publication-title: CA Cancer J Clin – volume: 13 start-page: 153 year: 2008 end-page: 166 article-title: Significance of CD90+ cancer stem cells in human liver cancer publication-title: Cancer Cell – volume: 9 start-page: 50 year: 2011 end-page: 63 article-title: CD24(+) liver tumor‐initiating cells drive self‐renewal and tumor initiation through STAT3‐mediated NANOG regulation publication-title: Cell Stem Cell – volume: 16 start-page: 1327 year: 1992 end-page: 1333 article-title: Occurrence of oval‐type cells in hepatitis B virus‐associated human hepatocarcinogenesis publication-title: HEPATOLOGY – volume: 106 start-page: 268 year: 2009 end-page: 273 article-title: The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem‐like cell populations publication-title: Proc Natl Acad Sci U S A – volume: 37 start-page: 19 year: 2005 end-page: 24 article-title: Dysregulation of the TSC‐mTOR pathway in human disease publication-title: Nat Genet – volume: 134 start-page: 215 year: 2008 end-page: 230 article-title: TGF‐β in cancer publication-title: Cell – volume: 204 start-page: 270 year: 1993 end-page: 279 article-title: Isolation, culture, and transplantation of rat hepatocytic precursor (stem‐like) cells publication-title: Proc Soc Exp Biol Med – volume: 54 start-page: 1259 year: 2011 end-page: 1272 article-title: Gankyrin‐mediated dedifferentiation facilitates the tumorigenicity of hepatocytes and hepatoma cells publication-title: HEPATOLOGY – volume: 56 start-page: 284 year: 2007 end-page: 292 article-title: Emerging insights into Transforming growth factor beta Smad signal in hepatic fibrogenesis publication-title: Gut – volume: 98 start-page: 6686 year: 2001 end-page: 6691 article-title: Genetic programs of epithelial cell plasticity directed by transforming growth factor‐beta publication-title: Proc Natl Acad Sci U S A – volume: 133 start-page: 647 year: 2007 end-page: 658 article-title: MicroRNA‐21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer publication-title: Gastroenterology – volume: 44 start-page: 240 year: 2006 end-page: 251 article-title: Side population purified from hepatocellular carcinoma cells harbors cancer stem cell‐like properties publication-title: HEPATOLOGY – volume: 115 start-page: 4715 year: 2010 end-page: 4724 article-title: An evolutionarily conserved PTEN‐C/EBPalpha‐CTNNA1 axis controls myeloid development and transformation publication-title: Blood – volume: 12 start-page: 9 year: 2007 end-page: 22 article-title: Defining the role of mTOR in cancer publication-title: Cancer Cell – volume: 241 start-page: 184 year: 2006 end-page: 196 article-title: PTEN function in normal and neoplastic growth publication-title: Cancer Lett – volume: 48 start-page: 2047 year: 2008 end-page: 2063 article-title: Molecular mechanisms of hepatocellular carcinoma publication-title: HEPATOLOGY – volume: 105 start-page: 2445 year: 2008 end-page: 2450 article-title: Progenitor/stem cells give rise to liver cancer due to aberrant TGF‐beta and IL‐6 signaling publication-title: Proc Natl Acad Sci U S A – volume: 68 start-page: 4287 year: 2008 end-page: 4295 article-title: Wnt/beta‐catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells publication-title: Cancer Res – volume: 51 start-page: 1373 year: 2010 end-page: 1382 article-title: Role of transforming growth factor beta signaling and expansion of progenitor cells in regenerating liver publication-title: HEPATOLOGY – volume: 371 start-page: 838 year: 2008 end-page: 851 article-title: Liver cirrhosis publication-title: Lancet – volume: 127 start-page: S35 year: 2004 end-page: S50 article-title: Hepatocellular carcinoma in cirrhosis: incidence and risk factors publication-title: Gastroenterology – volume: 454 start-page: 56 year: 2008 end-page: 61 article-title: SMAD proteins control DROSHA‐mediated microRNA maturation publication-title: Nature – volume: 27 start-page: 93 year: 2009 end-page: 101 article-title: Hypotheses on the role of transforming growth factor‐beta in the onset and progression of hepatocellular carcinoma publication-title: Dig Dis – volume: 30 start-page: 1425 year: 1999 end-page: 1433 article-title: The canals of Hering and hepatic stem cells in humans publication-title: HEPATOLOGY – volume: 131 start-page: 1109 year: 2007 end-page: 1123 article-title: let‐7 regulates self renewal and tumorigenicity of breast cancer cells publication-title: Cell – volume: 55 start-page: 108 year: 2012 end-page: 120 article-title: Hepatitis B Virus S (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine treated HBx transgenic mice publication-title: HEPATOLOGY – volume: 47 start-page: 2059 year: 2008 end-page: 2067 article-title: Transforming growth factor‐beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer publication-title: HEPATOLOGY – volume: 61 start-page: 6665 year: 2001 end-page: 6668 article-title: Heterozygous mice for the transforming growth factor‐beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis publication-title: Cancer Res – volume: 51 start-page: 1635 year: 2010 end-page: 1644 article-title: Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor‐beta publication-title: HEPATOLOGY – volume: 52 start-page: 1111 year: 2010 end-page: 1123 article-title: Bmi1 promotes hepatic stem cell expansion and tumorigenicity in both Ink4a/Arf‐dependent and ‐independent manners in mice publication-title: HEPATOLOGY – volume: 463 start-page: 676 year: 2010 end-page: 680 article-title: TGF‐beta‐FOXO signalling maintains leukaemia‐initiating cells in chronic myeloid leukaemia publication-title: Nature – volume: 49 start-page: 318 year: 2009 end-page: 329 article-title: Liver stem cells and hepatocellular carcinoma publication-title: HEPATOLOGY – volume: 24 start-page: 3028 year: 2005 end-page: 3041 article-title: Inactivation of TGF‐beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy publication-title: Oncogene – volume: 34 start-page: 859 year: 2001 end-page: 867 article-title: Transforming growth factor beta and the liver publication-title: HEPATOLOGY – volume: 445 start-page: 656 year: 2007 end-page: 660 article-title: Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas publication-title: Nature – volume: 45 start-page: 31 year: 2007 end-page: 41 article-title: Transforming growth factor‐beta differentially regulates oval cell and hepatocyte proliferation publication-title: HEPATOLOGY – volume: 284 start-page: 11755 year: 2009 end-page: 11759 article-title: PTEN, stem cells, and cancer stem cells publication-title: J Biol Chem – volume: 33 start-page: 179 year: 2001 end-page: 190 article-title: Chronic liver injury, TGF‐beta, and cancer publication-title: Exp Mol Med – volume: 116A start-page: 1 year: 2003 end-page: A10 article-title: TGF beta/Smad signaling system and its pathologic correlates publication-title: Am J Med Genet A – volume: 441 start-page: 475 year: 2006 end-page: 482 article-title: Pten dependence distinguishes haematopoietic stem cells from leukaemia‐initiating cells publication-title: Nature – volume: 24 start-page: 322 year: 2006 end-page: 332 article-title: Isolation and characterization of bipotent liver progenitor cells from adult mouse publication-title: Stem Cells – volume: 163 start-page: 723 year: 2003 end-page: 728 article-title: Cross‐talk between the Notch and TGF‐beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3 publication-title: J Cell Biol – volume: 53 start-page: 568 year: 2010 end-page: 577 article-title: Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications publication-title: J Hepatol – volume: 154 start-page: 38 year: 1984 end-page: 52 article-title: A diploid epithelial cell line from normal adult rat liver with phenotypic properties of ‘oval’ cells publication-title: Exp Cell Res – volume: 133 start-page: 937 year: 2007 ident: 10.1002/hep.26007-BIB10|cit10 article-title: Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation publication-title: Gastroenterology doi: 10.1053/j.gastro.2007.06.016 – volume: 35 start-page: 519 year: 2002 ident: 10.1002/hep.26007-BIB2|cit2 article-title: Prognostic prediction and treatment strategy in hepatocellular carcinoma publication-title: HEPATOLOGY doi: 10.1053/jhep.2002.32089 – volume: 3 start-page: 895 year: 2003 ident: 10.1002/hep.26007-BIB46|cit46 article-title: Applying the principles of stem-cell biology to cancer publication-title: Nat Rev Cancer doi: 10.1038/nrc1232 – volume: 27 start-page: 93 year: 2009 ident: 10.1002/hep.26007-BIB40|cit40 article-title: Hypotheses on the role of transforming growth factor-beta in the onset and progression of hepatocellular carcinoma publication-title: Dig Dis doi: 10.1159/000218340 – volume: 34 start-page: 859 year: 2001 ident: 10.1002/hep.26007-BIB17|cit17 article-title: Transforming growth factor beta and the liver publication-title: HEPATOLOGY doi: 10.1053/jhep.2001.28457 – volume: 49 start-page: 318 year: 2009 ident: 10.1002/hep.26007-BIB34|cit34 article-title: Liver stem cells and hepatocellular carcinoma publication-title: HEPATOLOGY doi: 10.1002/hep.22704 – volume: 241 start-page: 184 year: 2006 ident: 10.1002/hep.26007-BIB50|cit50 article-title: PTEN function in normal and neoplastic growth publication-title: Cancer Lett doi: 10.1016/j.canlet.2005.11.042 – volume: 12 start-page: 9 year: 2007 ident: 10.1002/hep.26007-BIB29|cit29 article-title: Defining the role of mTOR in cancer publication-title: Cancer Cell doi: 10.1016/j.ccr.2007.05.008 – volume: 13 start-page: 153 year: 2008 ident: 10.1002/hep.26007-BIB37|cit37 article-title: Significance of CD90+ cancer stem cells in human liver cancer publication-title: Cancer Cell doi: 10.1016/j.ccr.2008.01.013 – volume: 115 start-page: 209 year: 2005 ident: 10.1002/hep.26007-BIB32|cit32 article-title: Liver fibrosis publication-title: J Clin Invest doi: 10.1172/JCI24282 – volume: 12 start-page: 410 year: 2006 ident: 10.1002/hep.26007-BIB8|cit8 article-title: A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells publication-title: Nat Med doi: 10.1038/nm1377 – volume: 11 start-page: 881 year: 2009 ident: 10.1002/hep.26007-BIB31|cit31 article-title: TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN publication-title: Nat Cell Biol doi: 10.1038/ncb1897 – volume: 47 start-page: 2059 year: 2008 ident: 10.1002/hep.26007-BIB23|cit23 article-title: Transforming growth factor-beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer publication-title: HEPATOLOGY doi: 10.1002/hep.22283 – volume: 45 start-page: 31 year: 2007 ident: 10.1002/hep.26007-BIB45|cit45 article-title: Transforming growth factor-beta differentially regulates oval cell and hepatocyte proliferation publication-title: HEPATOLOGY doi: 10.1002/hep.21466 – volume: 54 start-page: 1259 year: 2011 ident: 10.1002/hep.26007-BIB22|cit22 article-title: Gankyrin-mediated dedifferentiation facilitates the tumorigenicity of hepatocytes and hepatoma cells publication-title: HEPATOLOGY doi: 10.1002/hep.24530 – volume: 127 start-page: S35 year: 2004 ident: 10.1002/hep.26007-BIB5|cit5 article-title: Hepatocellular carcinoma in cirrhosis: incidence and risk factors publication-title: Gastroenterology doi: 10.1053/j.gastro.2004.09.014 – volume: 5 start-page: 215 year: 2004 ident: 10.1002/hep.26007-BIB3|cit3 article-title: Focus on hepatocellular carcinoma publication-title: Cancer Cell doi: 10.1016/S1535-6108(04)00058-3 – volume: 163 start-page: 723 year: 2003 ident: 10.1002/hep.26007-BIB24|cit24 article-title: Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3 publication-title: J Cell Biol doi: 10.1083/jcb.200305112 – volume: 44 start-page: 240 year: 2006 ident: 10.1002/hep.26007-BIB38|cit38 article-title: Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties publication-title: HEPATOLOGY doi: 10.1002/hep.21227 – volume: 204 start-page: 270 year: 1993 ident: 10.1002/hep.26007-BIB19|cit19 article-title: Isolation, culture, and transplantation of rat hepatocytic precursor (stem-like) cells publication-title: Proc Soc Exp Biol Med doi: 10.3181/00379727-204-43663 – volume: 61 start-page: 6665 year: 2001 ident: 10.1002/hep.26007-BIB42|cit42 article-title: Heterozygous mice for the transforming growth factor-beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis publication-title: Cancer Res – volume: 9 start-page: 50 year: 2011 ident: 10.1002/hep.26007-BIB25|cit25 article-title: CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation publication-title: Cell Stem Cell doi: 10.1016/j.stem.2011.06.005 – volume: 61 start-page: 69 year: 2011 ident: 10.1002/hep.26007-BIB1|cit1 article-title: Global cancer statistics publication-title: CA Cancer J Clin doi: 10.3322/caac.20107 – volume: 134 start-page: 215 year: 2008 ident: 10.1002/hep.26007-BIB15|cit15 article-title: TGF-β in cancer publication-title: Cell doi: 10.1016/j.cell.2008.07.001 – volume: 51 start-page: 1373 year: 2010 ident: 10.1002/hep.26007-BIB44|cit44 article-title: Role of transforming growth factor beta signaling and expansion of progenitor cells in regenerating liver publication-title: HEPATOLOGY doi: 10.1002/hep.23449 – volume: 463 start-page: 676 year: 2010 ident: 10.1002/hep.26007-BIB28|cit28 article-title: TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia publication-title: Nature doi: 10.1038/nature08734 – volume: 115 start-page: 4715 year: 2010 ident: 10.1002/hep.26007-BIB52|cit52 article-title: An evolutionarily conserved PTEN-C/EBPalpha-CTNNA1 axis controls myeloid development and transformation publication-title: Blood doi: 10.1182/blood-2009-11-255778 – volume: 105 start-page: 2445 year: 2008 ident: 10.1002/hep.26007-BIB43|cit43 article-title: Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0705395105 – volume: 441 start-page: 475 year: 2006 ident: 10.1002/hep.26007-BIB53|cit53 article-title: Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells publication-title: Nature doi: 10.1038/nature04703 – volume: 98 start-page: 6686 year: 2001 ident: 10.1002/hep.26007-BIB16|cit16 article-title: Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.111614398 – volume: 27 start-page: 1749 year: 2008 ident: 10.1002/hep.26007-BIB26|cit26 article-title: CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway publication-title: Oncogene doi: 10.1038/sj.onc.1210811 – volume: 24 start-page: 3028 year: 2005 ident: 10.1002/hep.26007-BIB41|cit41 article-title: Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy publication-title: Oncogene doi: 10.1038/sj.onc.1208475 – volume: 24 start-page: 322 year: 2006 ident: 10.1002/hep.26007-BIB21|cit21 article-title: Isolation and characterization of bipotent liver progenitor cells from adult mouse publication-title: Stem Cells doi: 10.1634/stemcells.2005-0108 – volume: 128 start-page: 309 year: 2007 ident: 10.1002/hep.26007-BIB47|cit47 article-title: FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis publication-title: Cell doi: 10.1016/j.cell.2006.12.029 – volume: 48 start-page: 2047 year: 2008 ident: 10.1002/hep.26007-BIB35|cit35 article-title: Molecular mechanisms of hepatocellular carcinoma publication-title: HEPATOLOGY doi: 10.1002/hep.22580 – volume: 116A start-page: 1 year: 2003 ident: 10.1002/hep.26007-BIB13|cit13 article-title: TGF beta/Smad signaling system and its pathologic correlates publication-title: Am J Med Genet A doi: 10.1002/ajmg.a.10750 – volume: 154 start-page: 38 year: 1984 ident: 10.1002/hep.26007-BIB20|cit20 article-title: A diploid epithelial cell line from normal adult rat liver with phenotypic properties of ‘oval’ cells publication-title: Exp Cell Res doi: 10.1016/0014-4827(84)90666-9 – volume: 454 start-page: 56 year: 2008 ident: 10.1002/hep.26007-BIB56|cit56 article-title: SMAD proteins control DROSHA-mediated microRNA maturation publication-title: Nature doi: 10.1038/nature07086 – volume: 1 start-page: 101 year: 2007 ident: 10.1002/hep.26007-BIB48|cit48 article-title: Foxo3a is essential for maintenance of the hematopoietic stem cell pool publication-title: Cell Stem Cell doi: 10.1016/j.stem.2007.02.001 – volume: 131 start-page: 1109 year: 2007 ident: 10.1002/hep.26007-BIB55|cit55 article-title: let-7 regulates self renewal and tumorigenicity of breast cancer cells publication-title: Cell doi: 10.1016/j.cell.2007.10.054 – volume: 284 start-page: 11755 year: 2009 ident: 10.1002/hep.26007-BIB51|cit51 article-title: PTEN, stem cells, and cancer stem cells publication-title: J Biol Chem doi: 10.1074/jbc.R800071200 – volume: 37 start-page: 19 year: 2005 ident: 10.1002/hep.26007-BIB27|cit27 article-title: Dysregulation of the TSC-mTOR pathway in human disease publication-title: Nat Genet doi: 10.1038/ng1494 – volume: 445 start-page: 656 year: 2007 ident: 10.1002/hep.26007-BIB36|cit36 article-title: Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas publication-title: Nature doi: 10.1038/nature05529 – volume: 371 start-page: 838 year: 2008 ident: 10.1002/hep.26007-BIB4|cit4 article-title: Liver cirrhosis publication-title: Lancet doi: 10.1016/S0140-6736(08)60383-9 – volume: 106 start-page: 268 year: 2009 ident: 10.1002/hep.26007-BIB49|cit49 article-title: The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0810956106 – volume: 55 start-page: 108 year: 2012 ident: 10.1002/hep.26007-BIB11|cit11 article-title: Hepatitis B Virus S (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine treated HBx transgenic mice publication-title: HEPATOLOGY doi: 10.1002/hep.24675 – volume: 68 start-page: 4287 year: 2008 ident: 10.1002/hep.26007-BIB18|cit18 article-title: Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-07-6691 – volume: 16 start-page: 1327 year: 1992 ident: 10.1002/hep.26007-BIB7|cit7 article-title: Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis publication-title: HEPATOLOGY doi: 10.1002/hep.1840160604 – volume: 33 start-page: 179 year: 2001 ident: 10.1002/hep.26007-BIB14|cit14 article-title: Chronic liver injury, TGF-beta, and cancer publication-title: Exp Mol Med doi: 10.1038/emm.2001.31 – volume: 51 start-page: 1635 year: 2010 ident: 10.1002/hep.26007-BIB39|cit39 article-title: Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-beta publication-title: HEPATOLOGY doi: 10.1002/hep.23544 – volume: 133 start-page: 647 year: 2007 ident: 10.1002/hep.26007-BIB30|cit30 article-title: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer publication-title: Gastroenterology doi: 10.1053/j.gastro.2007.05.022 – volume: 53 start-page: 568 year: 2010 ident: 10.1002/hep.26007-BIB33|cit33 article-title: Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications publication-title: J Hepatol doi: 10.1016/j.jhep.2010.05.003 – volume: 30 start-page: 1425 year: 1999 ident: 10.1002/hep.26007-BIB6|cit6 article-title: The canals of Hering and hepatic stem cells in humans publication-title: HEPATOLOGY doi: 10.1002/hep.510300614 – volume: 56 start-page: 284 year: 2007 ident: 10.1002/hep.26007-BIB12|cit12 article-title: Emerging insights into Transforming growth factor beta Smad signal in hepatic fibrogenesis publication-title: Gut doi: 10.1136/gut.2005.088690 – volume: 116 start-page: 281 year: 2004 ident: 10.1002/hep.26007-BIB54|cit54 article-title: MicroRNAs: genomics, biogenesis, mechanism, and function publication-title: Cell doi: 10.1016/S0092-8674(04)00045-5 – volume: 52 start-page: 1111 year: 2010 ident: 10.1002/hep.26007-BIB9|cit9 article-title: Bmi1 promotes hepatic stem cell expansion and tumorigenicity in both Ink4a/Arf-dependent and -independent manners in mice publication-title: HEPATOLOGY doi: 10.1002/hep.23793 |
| SSID | ssj0009428 |
| Score | 2.499117 |
| Snippet | Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC... |
| SourceID | proquest pubmed pascalfrancis crossref wiley istex |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 2255 |
| SubjectTerms | AC133 Antigen Animals Antigens, CD - metabolism Antigens, Differentiation - metabolism Antigens, Neoplasm - metabolism Biological and medical sciences Biomarkers, Tumor - metabolism Cell Adhesion Molecules - metabolism Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology Diethylnitrosamine Epithelial Cell Adhesion Molecule Gastroenterology. Liver. Pancreas. Abdomen Glycoproteins - metabolism Hepatology Humans Liver - metabolism Liver cancer Liver cirrhosis Liver Cirrhosis - metabolism Liver Cirrhosis - pathology Liver Neoplasms, Experimental - chemically induced Liver Neoplasms, Experimental - metabolism Liver Neoplasms, Experimental - pathology Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID MicroRNAs - metabolism Neoplastic Stem Cells - metabolism Peptides - metabolism Pluripotent Stem Cells - drug effects Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - pathology Proteins Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism PTEN Phosphohydrolase - metabolism Rats Rats, Wistar STAT3 Transcription Factor - metabolism Thy-1 Antigens - metabolism TOR Serine-Threonine Kinases - metabolism Transforming Growth Factor beta - metabolism Transforming Growth Factor beta - pharmacology Tumors |
| Title | Hepatic transforming growth factor beta gives rise to tumor-initiating cells and promotes liver cancer development |
| URI | https://api.istex.fr/ark:/67375/WNG-X7ZW94V6-N/fulltext.pdf https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhep.26007 https://www.ncbi.nlm.nih.gov/pubmed/22898879 https://www.proquest.com/docview/1221565464 https://www.proquest.com/docview/1223432554 |
| Volume | 56 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1baxQxFD6UCuKL98toLVFEfJntTDq34JNI6yJ0EbF2ESEkmaSV1tllNwvikz_B3-gv8ZzMZVmpIL4N7MlCzpycfGfy5TsAz2pn8sypMnZFYuMsVyrWZZ3GeWpqYRB_W0MnukeTYnycvZ3m0y142d-FafUhhg9utDJCvqYFrvRyby0aembno6CujvmXuFoEiN6vpaNEFvqqYtWV0Omy6FWFEr43jNzYi66QW78RN1It0T2u7WtxGfDcxLFhIzq8AZ_7KbT8k_PRyuuR-f6HuuN_zvEmXO8AKnvVRtQt2LLNbbh61B3B3wE_tkTCNsz3kBc3P3aK1bw_Y233HqatV-yUBG0Z5hDL_Iz51dfZ4tePn1-IrKSIa83ozGDJVFOzeeAEovUFsUSYoUhcsHrNZ7oLx4cHH16P4651Q2ywAsK0VVQVNcJyaa1EmXBdpQaRkTYJd7mwqdYuddpUqlJYTwquROK0Frm2uUp0ku3fg-1m1tgHwLCCM6nCwtBUPHO1FcbgWCyETGrz_aKM4EX_EqXpdM2pvcaFbBWZuUQvyuDFCJ4OpvNWzOMyo-chEgYLtTgn9luZy5PJGzktP52I7GMhJxHsboTKMIAXiIEQGUSw08eO7DLDUqYcQRbdIMsieDL8jGuanK4aO1sFG7rvi0gvgvttzK3_HCtk3BgETjtEzt8nIscH78LDw383fQTXEBHylq-zA9t-sbKPEXV5vRuW1293oipT |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1baxQxFD7UFtQX75fRWqOI-DLbmencAr6Ito7aXURauwgSkkzSSuvssjsL4pM_wd_oL_GczGVZqSC-DczJQM6cJN9JvnwH4ElpdRJbmfk2DYwfJ1L6KitDPwl1yTXib6PpRHc4SovD-O04Ga_B8-4uTKMP0W-40chw8zUNcNqQ3l6qhp6Y6cDJq1-ADaroTfULXn1Yikfx2FVWxbwroPNl3ukKBdF233RlNdogx34jdqSco4NsU9niPOi5imTdUrR3FT53nWgYKKeDRa0G-vsf-o7_28trcKXFqOxFE1TXYc1UN-DisD2Fvwl1YYiHrVndoV5c_9gxJvT1CWsK-DBlasmOSdOW4TRiWD1h9eLrZPbrx88vxFeSRLdmdGwwZ7Iq2dTRAtH6jIgiTFMwzli5pDTdgsO93YOXhd9Wb_A1JkE4c6V5TrWwbFhKngWRykON4EjpILIJN6FSNrRK5zKXmFLySPLAKsUTZRIZqCDeuQ3r1aQyd4FhEqdDibmhzqPYloZrjW0xF9KhSXbSzINn3V8UupU2pwobZ6IRZY4EelE4L3rwuDedNnoe5xk9daHQW8jZKRHgskQcjV6LcfbpiMcfUzHyYGslVvoGUYowCMGBB5td8Ih2cpiLMEKcRZfIYg8e9a9xWJPTZWUmC2dDV34R7Hlwpwm65ccxSca1gWO3Xej8vSOi2H3vHu79u-lDuFQcDPfF_pvRu_twGQFi1NB3NmG9ni3MAwRhtdpyY-038sQubQ |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3bahRBEC1iAsEX75cxMbYi4stsZiZza_IkmnW9ZAlizBKEprunO5HE2WV3FoJP-QS_0S-xqueyrEQQ3wa2eqFrqrpPTZ8-BfC8sDqJrcx8mwbGjxMpfZUVoZ-EuuAa8bfRdKK7P0wHh_H7UTJagd32LkytD9F9cKPMcOs1JfiksNsL0dBTM-k5dfVrsBanmCyEiD4ttKN47BqrYtkV0PEyb2WFgmi7G7q0Ga2RXy-IHCln6B9bN7a4CnkuA1m3E_Vvwtd2DjUB5aw3r1RP__hD3vE_J3kLbjQIlb2qQ-o2rJjyDqzvN2fwd6EaGGJha1a1mBd3P3aC5Xx1yur2PUyZSrITUrRluIgYVo1ZNf8-nv66_PmN2EqSyNaMDg1mTJYFmzhSIFqfE02EaQrFKSsWhKZ7cNjf-_x64De9G3yNJRCuW2meUycsGxaSZ0Gk8lAjNFI6iGzCTaiUDa3SucwlFpQ8kjywSvFEmUQGKoh37sNqOS7NQ2BYwulQYmWo8yi2heFa41ishHRokp008-Bl-xKFboTNqb_GuaglmSOBXhTOix4860wntZrHVUYvXCR0FnJ6RvS3LBFHw7dilB0f8fhLKoYebC2FSjcgShEEITTwYLONHdEsDTMRRoiy6ApZ7MHT7mdManK6LM147mzowi9CPQ8e1DG3-HMskXFn4DhtFzl_n4gY7B24h0f_bvoE1g_e9MXHd8MPG3Ad0WFUc3c2YbWazs1jRGCV2nKZ9htsRS0l |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Hepatic+transforming+growth+factor+beta+gives+rise+to+tumor-initiating+cells+and+promotes+liver+cancer+development&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.au=Wu%2C+Kun&rft.au=Ding%2C+Jin&rft.au=Chen%2C+Cheng&rft.au=Sun%2C+Wen&rft.date=2012-12-01&rft.issn=1527-3350&rft.eissn=1527-3350&rft.volume=56&rft.issue=6&rft.spage=2255&rft_id=info:doi/10.1002%2Fhep.26007&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0270-9139&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0270-9139&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0270-9139&client=summon |