RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer

The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed in epithelial cancers, including gastric cancer. The aims of the present study were to evaluate whether RON affects tumor cell behaviors and oncogenic signaling pathways, and to document the relationship of its expr...

Full description

Saved in:

Bibliographic Details
Published in	Pathology international Vol. 62; no. 2; pp. 127 - 136
Main Authors	Song, Young-A., Park, Young-Lan, Kim, Kyu-Yeol, Myung, Eun, Chung, Cho-Yun, Cho, Sung-Bum, Lee, Wan-Sik, Jung, Young-Do, Kweon, Sun-Seog, Joo, Young-Eun
Format	Journal Article
Language	English
Published	Melbourne, Australia Blackwell Publishing Asia 01.02.2012
Subjects	Adult Aged Aged, 80 and over AKT protein Apoptosis Apoptosis - genetics Cell cycle Cell Cycle Checkpoints - genetics Cell Line, Tumor Cell migration cyclin D1 cyclin D3 Cyclin-dependent kinase 4 Disease Progression Female Gastric cancer Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Lymph nodes Male MAP kinase Middle Aged Neoplasm Invasiveness - genetics Phosphorylation Polymerase chain reaction Prognosis Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism Reverse transcription RON Ron protein Signal transduction Signal Transduction - genetics siRNA stomach neoplasm Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Tumor cell lines Tumor cells tumor metastasis Tumors
Online Access	Get full text

Cover

Loading…

Abstract	The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed in epithelial cancers, including gastric cancer. The aims of the present study were to evaluate whether RON affects tumor cell behaviors and oncogenic signaling pathways, and to document the relationship of its expression with various clinicopathological parameters in gastric cancer. The biological role of RON in tumor cell behaviors and oncogenic signaling pathways was investigated by using small interfering RNA in gastric cancer cell lines including AGS and MKN28. The expression of RON in gastric cancer tissues was investigated by using reverse transcription polymerase chain reaction and immunohistochemistry. Knockdown of RON suppressed tumor cell migration and invasion in AGS and MKN28, induced apoptosis through modulation of anti‐apoptotic and pre‐apoptotic genes and induced cell cycle arrest by decreasing cyclin D1, cyclin D3 and CDK4, and by inducing p21 and p27 expression. Signaling cascades, including Akt and mitogen‐activated protein kinase (MAPK), were significantly blocked by knockdown of RON. Expression of RON was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer.
AbstractList	The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed in epithelial cancers, including gastric cancer. The aims of the present study were to evaluate whether RON affects tumor cell behaviors and oncogenic signaling pathways, and to document the relationship of its expression with various clinicopathological parameters in gastric cancer. The biological role of RON in tumor cell behaviors and oncogenic signaling pathways was investigated by using small interfering RNA in gastric cancer cell lines including AGS and MKN28. The expression of RON in gastric cancer tissues was investigated by using reverse transcription polymerase chain reaction and immunohistochemistry. Knockdown of RON suppressed tumor cell migration and invasion in AGS and MKN28, induced apoptosis through modulation of anti‐apoptotic and pre‐apoptotic genes and induced cell cycle arrest by decreasing cyclin D1, cyclin D3 and CDK4, and by inducing p21 and p27 expression. Signaling cascades, including Akt and mitogen‐activated protein kinase (MAPK), were significantly blocked by knockdown of RON. Expression of RON was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer.
Author	Kim, Kyu-Yeol Joo, Young-Eun Song, Young-A. Park, Young-Lan Cho, Sung-Bum Kweon, Sun-Seog Myung, Eun Lee, Wan-Sik Jung, Young-Do Chung, Cho-Yun
Author_xml	– sequence: 1 givenname: Young-A. surname: Song fullname: Song, Young-A. organization: Departments of Internal Medicine – sequence: 2 givenname: Young-Lan surname: Park fullname: Park, Young-Lan organization: Departments of Internal Medicine – sequence: 3 givenname: Kyu-Yeol surname: Kim fullname: Kim, Kyu-Yeol organization: Departments of Internal Medicine – sequence: 4 givenname: Eun surname: Myung fullname: Myung, Eun organization: Departments of Internal Medicine – sequence: 5 givenname: Cho-Yun surname: Chung fullname: Chung, Cho-Yun organization: Departments of Internal Medicine – sequence: 6 givenname: Sung-Bum surname: Cho fullname: Cho, Sung-Bum organization: Departments of Internal Medicine – sequence: 7 givenname: Wan-Sik surname: Lee fullname: Lee, Wan-Sik organization: Departments of Internal Medicine – sequence: 8 givenname: Young-Do surname: Jung fullname: Jung, Young-Do organization: Biochemistry – sequence: 9 givenname: Sun-Seog surname: Kweon fullname: Kweon, Sun-Seog organization: Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea – sequence: 10 givenname: Young-Eun surname: Joo fullname: Joo, Young-Eun email: yejoo@chonnam.ac.kr organization: Departments of Internal Medicine
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/22243783$$D View this record in MEDLINE/PubMed
BookMark	eNqNkUtv1DAURi1URB_wF5B3sEnw286CBa1oqVRNoeKxtDyO0_GQxIPttDP_Hocps0R44yv7nOtrfafgaAyjAwBiVOOy3q1rzBiqsCKyJgjjGhEpeL19Bk4OF0elpgRVnAl6DE5TWiOEJRXoBTgmhDAqFT0BD3e3C-gTNCkF6012LXz0eQXzNIQINzHcR5eSDyN88AbmlYN-XPmlz_NR6KDZhE0Oae4wttC6vod2Z3sHTSxiLjRcTYMZ4b1JOXoLrRmtiy_B8870yb162s_At8uPXy8-VTe3V9cXH24qyxrCK-qY4UbJli0dlpYIQRrbso42DHEsG9R2VCmLGqMaLFohG9MyjhxxCptWEHoG3uz7lp_8mspAevBpntKMLkxJF4sTpBAu5Nt_khgRVUCFVUHVHrUxpBRdpzfRDybuCqTnfPRazzHoOQY956P_5KO3RX399Mq0HFx7EP8GUoD3e-DR927334315-vFXBW_2vs-Zbc9-Cb-1EJSyfWPxZXm598JP7_8ou_ob17Lr3A
CitedBy_id	crossref_primary_10_3892_ijo_2015_3157 crossref_primary_10_1038_s41523_018_0091_5 crossref_primary_10_1097_MPA_0000000000000088 crossref_primary_10_4068_cmj_2017_53_3_178 crossref_primary_10_3390_ijms17101633 crossref_primary_10_1038_s41598_019_54843_2 crossref_primary_10_1517_14728222_2012_710200 crossref_primary_10_1186_s12935_015_0157_5 crossref_primary_10_18632_aging_101945 crossref_primary_10_3892_ijo_2019_4717 crossref_primary_10_3892_ol_2018_8135 crossref_primary_10_3892_or_2016_4721 crossref_primary_10_1101_sqb_2016_81_031377 crossref_primary_10_4161_cbt_23718 crossref_primary_10_3892_ijo_2019_4836 crossref_primary_10_1007_s00432_016_2214_4 crossref_primary_10_3892_ol_2017_6696 crossref_primary_10_1371_journal_pone_0119229 crossref_primary_10_3892_or_2017_5356 crossref_primary_10_1007_s10565_020_09525_5 crossref_primary_10_1016_j_jos_2020_08_013
Cites_doi	10.4161/cbt.5.9.3073 10.1007/s10120-010-0561-4 10.1053/sarh.2003.50005 10.1163/2213441797X00073 10.1016/S0014-4827(03)00250-7 10.1111/j.1582-4934.2005.tb00337.x 10.1016/S0065-230X(08)00001-8 10.1016/j.canlet.2007.08.007 10.1038/374131a0 10.4161/cc.5.16.2864 10.1111/j.1745-7254.2006.00361.x 10.1007/978-1-60761-795-2_1 10.1007/978-3-642-83920-7 10.1245/ASO.2005.08.013 10.1093/carcin/bgg089 10.1517/14728222.2010.525221 10.4161/cbt.9.5.11217 10.2217/14796694.3.4.441 10.1165/ajrcmb.18.4.2978 10.1038/366704a0 10.1093/carcin/23.11.1811 10.1128/MMBR.00031-10 10.1186/1471-2407-8-353 10.1158/1078-0432.CCR-09-3064 10.2174/1568009033333745 10.1158/0008-5472.CAN-06-4128 10.1038/sj.bjc.6602593 10.1038/sj.onc.1201812 10.1006/excr.2000.5012 10.1158/0008-5472.CAN-03-3580 10.3233/BD-2007-26108 10.1593/tlo.10211 10.1038/nrc865 10.1002/bjs.7310 10.1517/13543784.2010.504709 10.1159/000320277
ContentType	Journal Article
Copyright	2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Copyright_xml	– notice: 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd – notice: 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
DBID	BSCLL CGR CUY CVF ECM EIF NPM AAYXX CITATION 8FD FR3 P64 RC3 7X8
DOI	10.1111/j.1440-1827.2011.02765.x
DatabaseName	Istex Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef Technology Research Database Engineering Research Database Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic
DatabaseTitle	MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef Genetics Abstracts Engineering Research Database Technology Research Database Biotechnology and BioEngineering Abstracts MEDLINE - Academic
DatabaseTitleList	CrossRef Genetics Abstracts MEDLINE MEDLINE - Academic
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	1440-1827
EndPage	136
ExternalDocumentID	10_1111_j_1440_1827_2011_02765_x 22243783 PIN2765 ark_67375_WNG_5BV25BFQ_R
Genre	article Research Support, Non-U.S. Gov't Journal Article
GroupedDBID	--- .3N .55 .GA .GJ .Y3 05W 0R~ 10A 123 1OB 1OC 29O 31~ 33P 36B 3O- 3SF 3UE 4.4 50Y 50Z 51W 51X 52M 52N 52O 52P 52R 52S 52T 52U 52V 52W 52X 53G 5HH 5LA 5VS 66C 702 7PT 8-0 8-1 8-3 8-4 8-5 8UM 930 A01 A03 AAESR AAEVG AAHHS AAHTB AAJUZ AANLZ AAONW AASGY AAVGM AAXRX AAZKR ABCQN ABCUV ABCVL ABDBF ABEML ABHUG ABJNI ABPEJ ABPTK ABPVW ABQWH ABXGK ACAHQ ACBWZ ACCFJ ACCZN ACGFS ACGOF ACIWK ACMXC ACPOU ACPRK ACSCC ACXBN ACXME ACXQS ADAWD ADBBV ADBTR ADDAD ADEOM ADIZJ ADKYN ADMGS ADOZA ADXAS ADZMN AEEZP AEGXH AEIGN AEIMD AENEX AEQDE AEQTP AEUQT AEUYR AFBPY AFEBI AFFPM AFGKR AFPWT AFRAH AFVGU AFZJQ AGJLS AHBTC AHEFC AIACR AIURR AIWBW AJBDE ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMYDB ATUGU AZBYB AZFZN AZVAB BAFTC BDRZF BFHJK BHBCM BMXJE BROTX BRXPI BSCLL BY8 C45 CAG COF CS3 D-6 D-7 D-E D-F DCZOG DPXWK DR2 DRFUL DRMAN DRSTM DU5 EAD EAP EBC EBD EBS EJD EMB EMK EMOBN ESX EX3 F00 F01 F04 F5P FEDTE FUBAC FZ0 G-S G.N GODZA GSXLS H.X HF~ HVGLF HZI HZ~ IHE IX1 J0M K48 KBYEO LATKE LC2 LC3 LEEKS LH4 LITHE LOXES LP6 LP7 LUTES LW6 LYRES MEWTI MK4 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM N04 N05 N9A NF~ O66 O9- OVD P2P P2W P2X P2Z P4B P4D PALCI Q.N Q11 QB0 R.K RIWAO RJQFR ROL RX1 SAMSI SUPJJ SV3 TEORI TUS UB1 V8K W8V W99 WBKPD WHWMO WIH WIJ WIK WOHZO WOW WQJ WRC WUP WVDHM WXI WXSBR X7M XG1 YFH YUY ZGI ZZTAW ~IA ~WT AITYG HGLYW OIG CGR CUY CVF ECM EIF NPM AAYXX CITATION 8FD FR3 P64 RC3 7X8
ID	FETCH-LOGICAL-c4925-3e4a5a87d4be17c26629cd4f394051790df388c09a8916d679ad450e2e81ad623
IEDL.DBID	DR2
ISSN	1320-5463
IngestDate	Fri Aug 16 08:36:35 EDT 2024 Fri Aug 16 11:59:18 EDT 2024 Fri Aug 23 03:39:16 EDT 2024 Thu May 23 23:15:07 EDT 2024 Sat Aug 24 00:53:51 EDT 2024 Wed Jan 17 05:01:47 EST 2024
IsPeerReviewed	true
IsScholarly	true
Issue	2
Language	English
License	2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c4925-3e4a5a87d4be17c26629cd4f394051790df388c09a8916d679ad450e2e81ad623
Notes	ark:/67375/WNG-5BV25BFQ-R istex:E482A3A0211CE728A8FA238B522F94C7A4874D29 ArticleID:PIN2765 These authors contributed equally to this work. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
PMID	22243783
PQID	1028080818
PQPubID	23462
PageCount	10
ParticipantIDs	proquest_miscellaneous_916520801 proquest_miscellaneous_1028080818 crossref_primary_10_1111_j_1440_1827_2011_02765_x pubmed_primary_22243783 wiley_primary_10_1111_j_1440_1827_2011_02765_x_PIN2765 istex_primary_ark_67375_WNG_5BV25BFQ_R
PublicationCentury	2000
PublicationDate	2012-02 February 2012 2012-Feb 2012-02-00 20120201
PublicationDateYYYYMMDD	2012-02-01
PublicationDate_xml	– month: 02 year: 2012 text: 2012-02
PublicationDecade	2010
PublicationPlace	Melbourne, Australia
PublicationPlace_xml	– name: Melbourne, Australia – name: Australia
PublicationTitle	Pathology international
PublicationTitleAlternate	Pathol Int
PublicationYear	2012
Publisher	Blackwell Publishing Asia
Publisher_xml	– name: Blackwell Publishing Asia
References	Cheng HL, Liu HS, Lin YJ et al. Coexpression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. Br J Cancer 2005; 92: 1906-14. Wang MH, Yao HP, Zhou YQ. Oncogenesis of RON receptor tyrosine kinase: A molecular target for malignant epithelial cancers. Acta Pharmacol Sin 2006; 27: 641-50. Peace BE, Toney-Earley K, Collins MH, Waltz SE. Ron receptor signaling augments mammary tumor formation and metastasis in a murine model of breast cancer. Cancer Res 2005; 65: 1285-93. Leonis MA, Thobe MN, Waltz SE. Ron-receptor tyrosine kinase in tumorigenesis and metastasis. Future Oncol 2007; 3: 441-8. Haagenson KK, Wu GS. Mitogen activated protein kinase phosphatases and cancer. Cancer Biol Ther 2010; 9: 337-40. Watanabe H, Jass JR, Sobin LH. WHO International Histologic Classification of Tumors: The Histologic Typing of Oesophageal and Gastric Tumors. Berlin, Heidelberg, New York, Paris, Tokyo, Hong Kong: Springer-Verlag, 1990. Schultz DR, Harrington WJ Jr. Apoptosis: Programmed cell death at a molecular level. Semin Arthritis Rheum 2003; 32: 345-69. Lauren P. The two histologic main types of gastric carcinoma. Acta Pathol Microbiol Scand 1965; 63: 31-49. Grana X, Reddy EP. Cell cycle control in mammalian cells: Role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 1995; 11: 211-9. Townson JL, Chambers AF. Dormancy of solitary metastatic cells. Cell Cycle 2006; 5: 1744-50. Sullivan RJ, Atkins MB. Molecular targeted therapy for patients with melanoma: The promise of MAPK pathway inhibition and beyond. Expert Opin Investig Drugs 2010; 19: 1205-16. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993; 366: 704-7. Pratilas CA, Solit DB. Targeting the mitogen-activated protein kinase pathway: Physiological feedback and drug response. Clin Cancer Res 2010; 16: 3329-34. Thomas RM, Toney K, Fenoglio-Preiser C et al. The RON receptor tyrosine kinase mediates oncogenic phenotypes in pancreatic cancer cells and is increasingly expressed during pancreatic cancer progression. Cancer Res 2007; 67: 6075-82. Wang MH, Wang D, Chen YQ. Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase. Carcinogenesis 2003; 24: 1291-300. Krejs GJ. Gastric cancer: Epidemiology and risk factors. Dig Dis 2010; 28: 600-3. Maggiora P, Marchio S, Stella MC, et al. Overexpression of the RON gene in human breast carcinoma. Oncogene 1998; 16: 2927-33. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 2011; 75: 50-83. Ahn HS, Lee HJ, Yoo MW et al. Changes in clinicopathological features and survival after gastrectomy for gastric cancer over a 20-year period. Br J Surg 2011; 98: 255-60. Gunes Z, Zucconi A, Cioce M et al. Isolation of fully human antagonistic antibodies showing efficient block of downstream signaling and cell migration. Trans Oncol 2011; 4: 38-46. Danilkovitch-Miagkova A. Oncogenic signaling pathways activated by RON receptor tyrosine kinase. Curr Cancer Drug Targets 2003; 3: 31-40. Zhou D, Pan G, Zheng C, Zheng J, Yian L, Teng X. Expression of the RON receptor tyrosine kinase and its association with gastric carcinoma versus normal gastric tissues. BMC Cancer 2008; 8: 353. Chen YQ, Zhou YQ, Fu LH, Wang D, Wang MH. Multiple pulmonary adenomas in the lung of transgenic mice overexpressing the RON receptor tyrosine kinase. Recepteur d'origine nantais. Carcinogenesis 2002; 23: 1811-19. Allan AL, Vantyghem SA, Tuck AB, Chambers AF. Tumor dormancy and cancer stem cells: Implications for the biology and treatment of breast cancer metastasis. Breast Dis 2006; 26: 87-98. Yao HP, Luo YL, Feng L et al. Agonistic monoclonal antibodies potentiate tumorigenic and invasive activities of splicing variant of the RON receptor tyrosine kinase. Cancer Biol Ther 2006; 5: 1179-86. Johnson N, Shapiro GI. Cyclin-dependent kinases (cdks) and the DNA damage response: Rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors. Expert Opin Ther Targets 2010; 14: 1199-212. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002; 2: 563-72. Maggiora P, Lorenzato A, Fracchioli S et al. The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. Exp Cell Res 2003; 288: 382-9. Camp ER, Liu W, Fan F, Yang A, Somcio R, Ellis LM. RON, a tyrosine kinase receptor involved in tumor progression and metastasis. Ann Surg Oncol 2005; 12: 273-81. Kuwahara A, Takachi R, Tsubono Y, Sasazuki S, Inoue M, Tsugane S, JPHC Study Group. Socioeconomic status and gastric cancer survival in Japan. Gastric Cancer 2010; 13: 222-30. Chen YQ, Zhou YQ, Angeloni D, Kurtz AL, Qiang XZ, Wang MH. Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines. Exp Cell Res 2000; 261: 229-38. Willett CG, Wang MH, Emanuel RL et al. Macrophage-stimulating protein and its receptor in non-small cell lung tumors: Induction of receptor tyrosine phosphorylation and cell migration. Am J Respir Cell Mol Biol 1998; 18: 489-96. Li Z, Yao H, Guin S, Padhye SS, Zhou YQ, Wang MH. Monoclonal antibodies-induced down-regulation of RON-receptor tyrosine kinase diminishes tumorigenic activities of colon cancer cells. Int J Oncol 2010; 37: 473-82. Keshet Y, Seger R. The MAP kinase signaling cascades: A system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 2010; 661: 3-38. Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 2005; 9: 59-71. Morgan DO. Principles of CDK regulation. Nature 1995; 374: 131-4. Lu Y, Yao HP, Wang MH. Multiple variants of the RON receptor tyrosine kinase: Biochemical properties, tumorigenic activities, and potential drug targets. Cancer Lett 2007; 257: 157-64. Wagh PK, Peace BE, Waltz SE. Met-related receptor tyrosine kinase Ron in tumor growth and metastasis. Adv Cancer Res 2008; 100: 1-33. 2010; 16 2010; 37 2010; 14 2010; 13 2010; 19 1995; 11 2011; 75 2002; 2 1997 2010; 661 2006; 5 2011; 98 2005; 65 2008; 8 2011; 4 1995; 374 2008; 100 1993; 366 2003; 32 2007; 257 1998; 16 1965; 63 1998; 18 1990 2010; 28 2006; 27 2002; 23 2005; 9 2006; 26 2003; 24 2003; 3 2000; 261 2005; 92 2007; 3 2003; 288 2007; 67 2005; 12 2010; 9 e_1_2_6_31_2 Li Z (e_1_2_6_25_2) 2010; 37 e_1_2_6_30_2 e_1_2_6_18_2 e_1_2_6_19_2 e_1_2_6_12_2 e_1_2_6_35_2 e_1_2_6_13_2 e_1_2_6_34_2 e_1_2_6_10_2 e_1_2_6_11_2 e_1_2_6_32_2 e_1_2_6_16_2 e_1_2_6_39_2 e_1_2_6_17_2 e_1_2_6_38_2 e_1_2_6_14_2 e_1_2_6_37_2 e_1_2_6_15_2 e_1_2_6_36_2 e_1_2_6_20_2 e_1_2_6_40_2 Lauren P (e_1_2_6_27_2) 1965; 63 e_1_2_6_8_2 e_1_2_6_7_2 e_1_2_6_9_2 e_1_2_6_29_2 e_1_2_6_4_2 e_1_2_6_3_2 e_1_2_6_6_2 e_1_2_6_5_2 e_1_2_6_24_2 e_1_2_6_23_2 e_1_2_6_2_2 e_1_2_6_22_2 e_1_2_6_21_2 e_1_2_6_28_2 e_1_2_6_26_2 Grana X (e_1_2_6_33_2) 1995; 11
References_xml	– volume: 366 start-page: 704 year: 1993 end-page: 7 article-title: A new regulatory motif in cell‐cycle control causing specific inhibition of cyclin D/CDK4 publication-title: Nature – volume: 8 start-page: 353 year: 2008 article-title: Expression of the RON receptor tyrosine kinase and its association with gastric carcinoma versus normal gastric tissues publication-title: BMC Cancer – volume: 65 start-page: 1285 year: 2005 end-page: 93 article-title: Ron receptor signaling augments mammary tumor formation and metastasis in a murine model of breast cancer publication-title: Cancer Res – volume: 37 start-page: 473 year: 2010 end-page: 82 article-title: Monoclonal antibodies‐induced down‐regulation of RON‐receptor tyrosine kinase diminishes tumorigenic activities of colon cancer cells publication-title: Int J Oncol – volume: 32 start-page: 345 year: 2003 end-page: 69 article-title: Apoptosis: Programmed cell death at a molecular level publication-title: Semin Arthritis Rheum – volume: 9 start-page: 337 year: 2010 end-page: 40 article-title: Mitogen activated protein kinase phosphatases and cancer publication-title: Cancer Biol Ther – volume: 3 start-page: 31 year: 2003 end-page: 40 article-title: Oncogenic signaling pathways activated by RON receptor tyrosine kinase publication-title: Curr Cancer Drug Targets – volume: 98 start-page: 255 year: 2011 end-page: 60 article-title: Changes in clinicopathological features and survival after gastrectomy for gastric cancer over a 20‐year period publication-title: Br J Surg – volume: 19 start-page: 1205 year: 2010 end-page: 16 article-title: Molecular targeted therapy for patients with melanoma: The promise of MAPK pathway inhibition and beyond publication-title: Expert Opin Investig Drugs – volume: 100 start-page: 1 year: 2008 end-page: 33 article-title: Met‐related receptor tyrosine kinase Ron in tumor growth and metastasis publication-title: Adv Cancer Res – volume: 23 start-page: 1811 year: 2002 end-page: 19 article-title: Multiple pulmonary adenomas in the lung of transgenic mice overexpressing the RON receptor tyrosine kinase. Recepteur d'origine nantais publication-title: Carcinogenesis – volume: 75 start-page: 50 year: 2011 end-page: 83 article-title: Activation and function of the MAPKs and their substrates, the MAPK‐activated protein kinases publication-title: Microbiol Mol Biol Rev – volume: 26 start-page: 87 year: 2006 end-page: 98 article-title: Tumor dormancy and cancer stem cells: Implications for the biology and treatment of breast cancer metastasis publication-title: Breast Dis – volume: 16 start-page: 2927 year: 1998 end-page: 33 article-title: Overexpression of the RON gene in human breast carcinoma publication-title: Oncogene – year: 1990 – volume: 27 start-page: 641 year: 2006 end-page: 50 article-title: Oncogenesis of RON receptor tyrosine kinase: A molecular target for malignant epithelial cancers publication-title: Acta Pharmacol Sin – volume: 5 start-page: 1179 year: 2006 end-page: 86 article-title: Agonistic monoclonal antibodies potentiate tumorigenic and invasive activities of splicing variant of the RON receptor tyrosine kinase publication-title: Cancer Biol Ther – volume: 288 start-page: 382 year: 2003 end-page: 9 article-title: The RON and MET oncogenes are co‐expressed in human ovarian carcinomas and cooperate in activating invasiveness publication-title: Exp Cell Res – volume: 24 start-page: 1291 year: 2003 end-page: 300 article-title: Oncogenic and invasive potentials of human macrophage‐stimulating protein receptor, the RON receptor tyrosine kinase publication-title: Carcinogenesis – volume: 9 start-page: 59 year: 2005 end-page: 71 article-title: The activation of Akt/PKB signaling pathway and cell survival publication-title: J Cell Mol Med – volume: 4 start-page: 38 year: 2011 end-page: 46 article-title: Isolation of fully human antagonistic antibodies showing efficient block of downstream signaling and cell migration publication-title: Trans Oncol – volume: 28 start-page: 600 year: 2010 end-page: 3 article-title: Gastric cancer: Epidemiology and risk factors publication-title: Dig Dis – start-page: 71 year: 1997 end-page: 6 – volume: 3 start-page: 441 year: 2007 end-page: 8 article-title: Ron‐receptor tyrosine kinase in tumorigenesis and metastasis publication-title: Future Oncol – volume: 92 start-page: 1906 year: 2005 end-page: 14 article-title: Coexpression of RON and MET is a prognostic indicator for patients with transitional‐cell carcinoma of the bladder publication-title: Br J Cancer – volume: 2 start-page: 563 year: 2002 end-page: 72 article-title: Dissemination and growth of cancer cells in metastatic sites publication-title: Nat Rev Cancer – volume: 18 start-page: 489 year: 1998 end-page: 96 article-title: Macrophage‐stimulating protein and its receptor in non‐small cell lung tumors: Induction of receptor tyrosine phosphorylation and cell migration publication-title: Am J Respir Cell Mol Biol – volume: 67 start-page: 6075 year: 2007 end-page: 82 article-title: The RON receptor tyrosine kinase mediates oncogenic phenotypes in pancreatic cancer cells and is increasingly expressed during pancreatic cancer progression publication-title: Cancer Res – volume: 13 start-page: 222 year: 2010 end-page: 30 article-title: Socioeconomic status and gastric cancer survival in Japan publication-title: Gastric Cancer – volume: 5 start-page: 1744 year: 2006 end-page: 50 article-title: Dormancy of solitary metastatic cells publication-title: Cell Cycle – volume: 257 start-page: 157 year: 2007 end-page: 64 article-title: Multiple variants of the RON receptor tyrosine kinase: Biochemical properties, tumorigenic activities, and potential drug targets publication-title: Cancer Lett – volume: 63 start-page: 31 year: 1965 end-page: 49 article-title: The two histologic main types of gastric carcinoma publication-title: Acta Pathol Microbiol Scand – volume: 12 start-page: 273 year: 2005 end-page: 81 article-title: RON, a tyrosine kinase receptor involved in tumor progression and metastasis publication-title: Ann Surg Oncol – volume: 374 start-page: 131 year: 1995 end-page: 4 article-title: Principles of CDK regulation publication-title: Nature – volume: 16 start-page: 3329 year: 2010 end-page: 34 article-title: Targeting the mitogen‐activated protein kinase pathway: Physiological feedback and drug response publication-title: Clin Cancer Res – volume: 661 start-page: 3 year: 2010 end-page: 38 article-title: The MAP kinase signaling cascades: A system of hundreds of components regulates a diverse array of physiological functions publication-title: Methods Mol Biol – volume: 11 start-page: 211 year: 1995 end-page: 9 article-title: Cell cycle control in mammalian cells: Role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin‐dependent kinase inhibitors (CKIs) publication-title: Oncogene – volume: 261 start-page: 229 year: 2000 end-page: 38 article-title: Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines publication-title: Exp Cell Res – volume: 14 start-page: 1199 year: 2010 end-page: 212 article-title: Cyclin‐dependent kinases (cdks) and the DNA damage response: Rationale for cdk inhibitor‐chemotherapy combinations as an anticancer strategy for solid tumors publication-title: Expert Opin Ther Targets – ident: e_1_2_6_9_2 doi: 10.4161/cbt.5.9.3073 – ident: e_1_2_6_2_2 doi: 10.1007/s10120-010-0561-4 – ident: e_1_2_6_31_2 doi: 10.1053/sarh.2003.50005 – ident: e_1_2_6_29_2 doi: 10.1163/2213441797X00073 – ident: e_1_2_6_21_2 doi: 10.1016/S0014-4827(03)00250-7 – ident: e_1_2_6_30_2 doi: 10.1111/j.1582-4934.2005.tb00337.x – ident: e_1_2_6_14_2 doi: 10.1016/S0065-230X(08)00001-8 – ident: e_1_2_6_8_2 doi: 10.1016/j.canlet.2007.08.007 – ident: e_1_2_6_32_2 doi: 10.1038/374131a0 – ident: e_1_2_6_6_2 doi: 10.4161/cc.5.16.2864 – ident: e_1_2_6_12_2 doi: 10.1111/j.1745-7254.2006.00361.x – ident: e_1_2_6_37_2 doi: 10.1007/978-1-60761-795-2_1 – ident: e_1_2_6_28_2 doi: 10.1007/978-3-642-83920-7 – ident: e_1_2_6_11_2 doi: 10.1245/ASO.2005.08.013 – ident: e_1_2_6_13_2 doi: 10.1093/carcin/bgg089 – volume: 11 start-page: 211 year: 1995 ident: e_1_2_6_33_2 article-title: Cell cycle control in mammalian cells: Role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin‐dependent kinase inhibitors (CKIs) publication-title: Oncogene contributor: fullname: Grana X – ident: e_1_2_6_35_2 doi: 10.1517/14728222.2010.525221 – ident: e_1_2_6_40_2 doi: 10.4161/cbt.9.5.11217 – ident: e_1_2_6_10_2 doi: 10.2217/14796694.3.4.441 – ident: e_1_2_6_20_2 doi: 10.1165/ajrcmb.18.4.2978 – ident: e_1_2_6_34_2 doi: 10.1038/366704a0 – ident: e_1_2_6_16_2 doi: 10.1093/carcin/23.11.1811 – ident: e_1_2_6_36_2 doi: 10.1128/MMBR.00031-10 – ident: e_1_2_6_23_2 doi: 10.1186/1471-2407-8-353 – ident: e_1_2_6_39_2 doi: 10.1158/1078-0432.CCR-09-3064 – ident: e_1_2_6_15_2 doi: 10.2174/1568009033333745 – ident: e_1_2_6_22_2 doi: 10.1158/0008-5472.CAN-06-4128 – ident: e_1_2_6_24_2 doi: 10.1038/sj.bjc.6602593 – ident: e_1_2_6_19_2 doi: 10.1038/sj.onc.1201812 – ident: e_1_2_6_18_2 doi: 10.1006/excr.2000.5012 – volume: 63 start-page: 31 year: 1965 ident: e_1_2_6_27_2 article-title: The two histologic main types of gastric carcinoma publication-title: Acta Pathol Microbiol Scand contributor: fullname: Lauren P – ident: e_1_2_6_17_2 doi: 10.1158/0008-5472.CAN-03-3580 – ident: e_1_2_6_5_2 doi: 10.3233/BD-2007-26108 – ident: e_1_2_6_26_2 doi: 10.1593/tlo.10211 – ident: e_1_2_6_7_2 doi: 10.1038/nrc865 – ident: e_1_2_6_4_2 doi: 10.1002/bjs.7310 – ident: e_1_2_6_38_2 doi: 10.1517/13543784.2010.504709 – ident: e_1_2_6_3_2 doi: 10.1159/000320277 – volume: 37 start-page: 473 year: 2010 ident: e_1_2_6_25_2 article-title: Monoclonal antibodies‐induced down‐regulation of RON‐receptor tyrosine kinase diminishes tumorigenic activities of colon cancer cells publication-title: Int J Oncol contributor: fullname: Li Z
SSID	ssj0017360
Score	2.1232886
Snippet	The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed in epithelial cancers, including gastric cancer. The aims of the present study...
SourceID	proquest crossref pubmed wiley istex
SourceType	Aggregation Database Index Database Publisher
StartPage	127
SubjectTerms	Adult Aged Aged, 80 and over AKT protein Apoptosis Apoptosis - genetics Cell cycle Cell Cycle Checkpoints - genetics Cell Line, Tumor Cell migration cyclin D1 cyclin D3 Cyclin-dependent kinase 4 Disease Progression Female Gastric cancer Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Lymph nodes Male MAP kinase Middle Aged Neoplasm Invasiveness - genetics Phosphorylation Polymerase chain reaction Prognosis Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism Reverse transcription RON Ron protein Signal transduction Signal Transduction - genetics siRNA stomach neoplasm Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Tumor cell lines Tumor cells tumor metastasis Tumors
Title	RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer
URI	https://api.istex.fr/ark:/67375/WNG-5BV25BFQ-R/fulltext.pdf https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1440-1827.2011.02765.x https://www.ncbi.nlm.nih.gov/pubmed/22243783 https://search.proquest.com/docview/1028080818 https://search.proquest.com/docview/916520801
Volume	62
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
link	http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3db9MwED-hISFe-IaFDXRIiLdUiWPn43FDKwNpBSoGe7P8VaiqJVWbToO_Hp-TFjoNCSHerMgf8fnO_tk-_w7gJU-VXxe5iMvKupg7m8SVYjr2mw0hbGWEzejt8MkoPz7l787EWe__RG9hOn6IzYEbWUaYr8nAlV5eMfJwL8mKnomTFbkYEJ4kXj3CR-MNk1RaZL8eDBMD_LZTz7UVba1UN0nol9fB0G1UG5al4V2YrTvUeaPMBqtWD8yPK1yP_6fH9-BOj17xoFO3-3DD1Q_g1kl_P_8QLsbvRzhdouoH3Vmkg15sV-fNAoMvWMcDghdThR574rT-NtXBbQybCap5M2-bJdVQW6RLBTTffUuoQgwRnxtDUEH8qijeiEFDSrt4BKfDo0-vj-M-skNsiAwxzhxXQpWF5dqlhfEggVXG8gmFaQ-cYXaSlaVJKlV6-GrzolKWi8QxV6bKesT2GHbqpna7gKoQJk-s30UmnDs__6pM67TShjGTiGQSQboeRTnvCDzk7xsf7tNeoJIEKoNA5WUEr8JwbwqoxYwc4Aohv4zeSHH4mYnD4Uc5juDFWh-kN0sSi6pds1pKwm0JRTUpI8A_5PFdE8xnSiN40unSpkGP2nhWlFkEedCIv_51-eHtiFJP_7XgHtz2n1nnmL4PO-1i5Z553NXq58GifgJSWBzC
link.rule.ids	315,786,790,1382,27957,27958,46329,46753
linkProvider	Wiley-Blackwell
linkToHtml	http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3db9MwELfQJgEvfDPC5yEh3lIljp2PR4boOlgLVBvszXJsF6pBUrXpNPjruXPSjk5DQoi3PJzt-Hxn_2yff8fYCxFrXBeFDPPCulA4G4WF5mWImw0pbWGkTejt8HCUDo7E22N53KUDorcwLT_E-sCNPMPP1-TgdCB9wcv9xSTPOipOnqWyh4ByG71f-v3VeM0lFWfJ-ZNh4oDfDOu5tKaNtWqb1H52GRDdxLV-YerfZN9WXWrjUU56y6bsmZ8X2B7_U59vsRsdgIVXrcXdZldcdYddHXZX9HfZ6fj9CKYL0N24Owt01gvN8ns9Bx8O1lKBwOlUA8JPmFZfp6WPHIN6AnpWz5p6QTVUFuheAcwPbAm0TyOC0uDzCsIXTSlHDBiy2_k9dtR_c_h6EHbJHUJDfIhh4oSWOs-sKF2cGcQJvDBWTChTu6cNs5Mkz01U6BwRrE2zQlshI8ddHmuLoO0-26rqyj1goDNp0sjiRjISwuEUrJOyjIvScG4iGU0CFq-GUc1aDg_1-95H4DcqVJFClVeoOgvYSz_e6wJ6fkIxcJlUn0d7Su5-4nK3_1GNA_Z8ZRAKPZPUoitXLxeKoFtEiU3ygMEfZLBrkqNQHLCd1pjWDSJwE0mWJwFLvUn89a-rD_sj-nr4rwWfsWuDw-GBOtgfvXvErqMIb-PUH7OtZr50TxCGNeVT716_AD6bIOQ
linkToPdf	http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwEB6hVqq48IaG5yAhblkljp3HkVKWFmgoKwq9WY7twGpFstpHVfj1eJzswlZFQohbDmM7Hs_Yn-3xNwDPeKzcushFmBfGhtyaKCwUq0K32RDCFFqYhN4OH5XpwQl_cypO-_gnegvT8UOsD9zIM_x8TQ4-NfUFJ_f3kizrmThZloqBw5PbPE0YWfj-aE0lFWfJrxfDRAG_GdVzaU0bS9U2af38Mhy6CWv9ujS8DpNVj7pwlMlguagG-scFssf_0-UbcK2Hr_iis7ebcMU2t2DnqL-gvw1no_cljueo-lG3BumkFxfLb-0MfTBYRwSCZ2OFDnziuPk6rnzcGLY1qmk7XbRzqqExSLcKqL-7llD5JCJOGn1WQfyiKOGIRk1WO7sDJ8NXH18ehH1qh1ATG2KYWK6EyjPDKxtn2qEEVmjDa8rT7knDTJ3kuY4KlTv8atKsUIaLyDKbx8o4yHYXtpq2sbuAKhM6jYzbRkacWzcBq6Sq4qLSjOlIRHUA8WoU5bRj8JC_73y4-3YKlaRQ6RUqzwN47od7XUDNJhQBlwn5uXwtxd4nJvaGH-QogKcre5DOL0ktqrHtci4JuEWU1iQPAP8g47ommBOKA7jX2dK6QQfbeJLlSQCpt4i__nV5fFjS1_1_LfgEdo73h_LdYfn2AVx1EqwLUn8IW4vZ0j5yGGxRPfbO9ROtAR-T
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=RON+is+associated+with+tumor+progression+via+the+inhibition+of+apoptosis+and+cell+cycle+arrest+in+human+gastric+cancer&rft.jtitle=Pathology+international&rft.au=Song%2C+Young-A&rft.au=Park%2C+Young-Lan&rft.au=Kim%2C+Kyu-Yeol&rft.au=Myung%2C+Eun&rft.date=2012-02-01&rft.issn=1320-5463&rft.eissn=1440-1827&rft.volume=62&rft.issue=2&rft.spage=127&rft.epage=136&rft_id=info:doi/10.1111%2Fj.1440-1827.2011.02765.x&rft.externalDBID=NO_FULL_TEXT
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1320-5463&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1320-5463&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1320-5463&client=summon