Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression

The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HM...

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Published inCancers Vol. 12; no. 5; p. 1088
Main Authors Wang, I-Han, Huang, Tzu-Ting, Chen, Ji-Lin, Chu, Li-Wei, Ping, Yueh-Hsin, Hsu, Kai-Wen, Huang, Kuo-Hung, Fang, Wen-Liang, Lee, Hsin-Chen, Chen, Chian-Feng, Liao, Chen-Chung, Hsieh, Rong-Hong, Yeh, Tien-Shun
Format Journal Article
LanguageEnglish
Published Switzerland MDPI 27.04.2020
MDPI AG
Subjects
gastric cancer progression
HMGCS1
integrated stress response
mevalonate pathway
pluripotency
mevalonate pathway
pluripotency
HMGCS1
gastric cancer progression
integrated stress response
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Abstract The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.
AbstractList The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.
Author Hsieh, Rong-Hong
Chen, Ji-Lin
Hsu, Kai-Wen
Lee, Hsin-Chen
Wang, I-Han
Huang, Tzu-Ting
Chu, Li-Wei
Liao, Chen-Chung
Ping, Yueh-Hsin
Fang, Wen-Liang
Huang, Kuo-Hung
Chen, Chian-Feng
Yeh, Tien-Shun
AuthorAffiliation 2 Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan; tzu-ting.huang@nih.gov (T.-T.H.); Jlchen_@outlook.com (J.-L.C.)
9 Proteomics Research Center, National Yang-Ming University, Taipei 112, Taiwan; ccliao@ym.edu.tw
11 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan
6 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan; khhuang@vghtpe.gov.tw (K.-H.H.); wlfang@vghtpe.gov.tw (W.-L.F.)
10 School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110, Taiwan; hsiehrh@tmu.edu.tw
5 Graduate Institutes of New Drug Development, China Medical University, Taichung 404, Taiwan
8 Cancer Progression Research Center, National Yang-Ming University, Taipei 112, Taiwan; cfchen@ym.edu.tw
12 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
3 Department and Inst
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Cites_doi 10.1016/j.bbalip.2013.03.003
10.1159/000185525
10.1091/mbc.e09-05-0386
10.1172/JCI11596
10.1016/j.bbagrm.2014.10.002
10.1158/0008-5472.CAN-08-4021
10.1074/jbc.M110.134213
10.1038/16729
10.1016/j.molcel.2017.06.017
10.1371/journal.pbio.0040374
10.1158/0008-5472.CAN-12-4085
10.1074/jbc.M301408200
10.18632/oncotarget.9342
10.1158/1078-0432.CCR-12-0859
10.1016/j.stem.2009.05.021
10.1074/mcp.M111.013284
10.1038/343425a0
10.18632/oncotarget.2073
10.1126/science.1175371
10.1016/j.cell.2011.12.017
10.1038/onc.2014.320
10.1002/stem.1122
10.1038/ajg.2011.277
10.1073/pnas.1414748111
10.1007/s10856-010-4014-8
10.1158/0008-5472.CAN-14-0130
10.1002/mc.20865
10.1073/pnas.0910258107
10.15252/embr.201642195
10.1074/mcp.M112.017905
10.1002/ijc.29210
10.1172/JCI62973
10.1038/ncb1471
10.1038/s41556-019-0347-9
10.1016/j.toxlet.2012.02.017
10.1016/j.molcel.2011.08.025
10.1074/jbc.R113.479808
10.1016/j.bbcan.2020.188351
10.18632/aging.100339
10.1182/blood-2009-07-230508
10.1371/journal.pone.0148818
10.1158/1535-7163.MCT-19-0413
10.18632/oncotarget.4817
10.1126/science.1231143
10.1128/MCB.00175-08
10.1038/ncb2738
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Issue 5
Keywords mevalonate pathway
pluripotency
HMGCS1
gastric cancer progression
integrated stress response
Language English
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Present address: Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei 112, Taiwan; Jlchen_@outlook.com.
These authors contributed equally to this paper.
Present address: Women’s Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; tzu-ting.huang@nih.gov.
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References Nielsen (ref_8) 2013; 368
Hetz (ref_27) 2018; 69
Chang (ref_41) 2013; 73
Drynda (ref_16) 2010; 21
Tamada (ref_23) 2012; 18
Tameire (ref_33) 2019; 21
Goldstein (ref_5) 1990; 343
Hartman (ref_24) 2010; 285
Munoz (ref_35) 2009; 5
Sharpe (ref_6) 2013; 288
Gobel (ref_10) 2020; 1873
Mizuno (ref_15) 2012; 148
Hsu (ref_47) 2016; 7
Hart (ref_31) 2012; 122
Cong (ref_21) 2013; 339
Chiu (ref_9) 2011; 106
Clendening (ref_11) 2010; 115
Hsu (ref_45) 2008; 28
Wang (ref_44) 2014; 5
Ginestier (ref_4) 2012; 30
Harding (ref_28) 1999; 397
Wagner (ref_38) 2011; 10
Hsu (ref_43) 2009; 20
Pandyra (ref_19) 2015; 6
Koryga (ref_26) 2016; 17
Clendening (ref_3) 2010; 107
Sapir (ref_7) 2014; 111
Dubey (ref_18) 2015; 1849
Ohashi (ref_25) 2003; 278
Thurnher (ref_2) 2013; 1831
Ferlay (ref_1) 2015; 136
Lee (ref_34) 2012; 211
Vock (ref_12) 2008; 22
Werstuck (ref_17) 2001; 107
ref_20
Kim (ref_37) 2011; 44
Wagner (ref_39) 2012; 11
Lincet (ref_22) 2015; 34
Zhou (ref_14) 2020; 19
Yeh (ref_42) 2009; 69
ref_29
Choudhary (ref_36) 2009; 325
Denoyelle (ref_32) 2006; 8
Tseng (ref_46) 2012; 51
Han (ref_30) 2013; 15
Pandyra (ref_13) 2014; 74
Hirschey (ref_40) 2011; 3
References_xml – volume: 1831
  start-page: 1009
  year: 2013
  ident: ref_2
  article-title: Regulation of mevalonate metabolism in cancer and immune cells
  publication-title: Biochim. Biophys. Acta
  doi: 10.1016/j.bbalip.2013.03.003
  contributor:
    fullname: Thurnher
– volume: 22
  start-page: 515
  year: 2008
  ident: ref_12
  article-title: Transcriptional regulation of HMG-CoA synthase and HMG-CoA reductase genes by human ACBP
  publication-title: Cell. Physiol. Biochem.
  doi: 10.1159/000185525
  contributor:
    fullname: Vock
– volume: 20
  start-page: 5127
  year: 2009
  ident: ref_43
  article-title: MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2
  publication-title: Mol. Biol. Cell
  doi: 10.1091/mbc.e09-05-0386
  contributor:
    fullname: Hsu
– volume: 107
  start-page: 1263
  year: 2001
  ident: ref_17
  article-title: Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways
  publication-title: J. Clin. Investig.
  doi: 10.1172/JCI11596
  contributor:
    fullname: Werstuck
– volume: 1849
  start-page: 32
  year: 2015
  ident: ref_18
  article-title: STAT6 silencing up-regulates cholesterol synthesis via miR-197/FOXJ2 axis and induces ER stress-mediated apoptosis in lung cancer cells
  publication-title: Biochim. Biophys. Acta
  doi: 10.1016/j.bbagrm.2014.10.002
  contributor:
    fullname: Dubey
– volume: 69
  start-page: 5039
  year: 2009
  ident: ref_42
  article-title: The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-08-4021
  contributor:
    fullname: Yeh
– volume: 285
  start-page: 19288
  year: 2010
  ident: ref_24
  article-title: Sterol-induced dislocation of 3-hydroxy-3-methylglutaryl coenzyme A reductase from endoplasmic reticulum membranes into the cytosol through a subcellular compartment resembling lipid droplets
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M110.134213
  contributor:
    fullname: Hartman
– volume: 397
  start-page: 271
  year: 1999
  ident: ref_28
  article-title: Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
  publication-title: Nature
  doi: 10.1038/16729
  contributor:
    fullname: Harding
– volume: 69
  start-page: 169
  year: 2018
  ident: ref_27
  article-title: The unfolded protein response and cell fate control
  publication-title: Mol. Cell.
  doi: 10.1016/j.molcel.2017.06.017
  contributor:
    fullname: Hetz
– ident: ref_29
  doi: 10.1371/journal.pbio.0040374
– volume: 73
  start-page: 4147
  year: 2013
  ident: ref_41
  article-title: Connective tissue growth factor activates pluripotency genes and mesenchymal-epithelial transition in head and neck cancer cells
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-12-4085
  contributor:
    fullname: Chang
– volume: 278
  start-page: 36819
  year: 2003
  ident: ref_25
  article-title: Localization of mammalian NAD(P)H steroid dehydrogenase-like protein on lipid droplets
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M301408200
  contributor:
    fullname: Ohashi
– volume: 7
  start-page: 38036
  year: 2016
  ident: ref_47
  article-title: Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.9342
  contributor:
    fullname: Hsu
– volume: 18
  start-page: 5554
  year: 2012
  ident: ref_23
  article-title: Pyruvate kinase M2: Multiple faces for conferring benefits on cancer cells
  publication-title: Clin. Cancer Res.
  doi: 10.1158/1078-0432.CCR-12-0859
  contributor:
    fullname: Tamada
– volume: 5
  start-page: 214
  year: 2009
  ident: ref_35
  article-title: Phosphorylation dynamics during early differentiation of human embryonic stem cells
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2009.05.021
  contributor:
    fullname: Munoz
– volume: 10
  start-page: M111.013284
  year: 2011
  ident: ref_38
  article-title: A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles
  publication-title: Mol. Cell Proteom.
  doi: 10.1074/mcp.M111.013284
  contributor:
    fullname: Wagner
– volume: 343
  start-page: 425
  year: 1990
  ident: ref_5
  article-title: Regulation of the mevalonate pathway
  publication-title: Nature
  doi: 10.1038/343425a0
  contributor:
    fullname: Goldstein
– volume: 5
  start-page: 5002
  year: 2014
  ident: ref_44
  article-title: Yin Yang 1 is a target of microRNA-34 family and contributes to gastric carcinogenesis
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.2073
  contributor:
    fullname: Wang
– volume: 325
  start-page: 834
  year: 2009
  ident: ref_36
  article-title: Lysine acetylation targets protein complexes and co-regulates major cellular functions
  publication-title: Science
  doi: 10.1126/science.1175371
  contributor:
    fullname: Choudhary
– volume: 148
  start-page: 244
  year: 2012
  ident: ref_15
  article-title: Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway
  publication-title: Cell
  doi: 10.1016/j.cell.2011.12.017
  contributor:
    fullname: Mizuno
– volume: 34
  start-page: 3751
  year: 2015
  ident: ref_22
  article-title: How do glycolytic enzymes favour cancer cell proliferation by nonmetabolic functions?
  publication-title: Oncogene
  doi: 10.1038/onc.2014.320
  contributor:
    fullname: Lincet
– volume: 30
  start-page: 1327
  year: 2012
  ident: ref_4
  article-title: Mevalonate metabolism regulates Basal breast cancer stem cells and is a potential therapeutic target
  publication-title: Stem Cells
  doi: 10.1002/stem.1122
  contributor:
    fullname: Ginestier
– volume: 106
  start-page: 2098
  year: 2011
  ident: ref_9
  article-title: Statins are associated with a reduced risk of gastric cancer: A population-based case-control study
  publication-title: Am. J. Gastroenterol.
  doi: 10.1038/ajg.2011.277
  contributor:
    fullname: Chiu
– volume: 111
  start-page: E3880
  year: 2014
  ident: ref_7
  article-title: Controlled sumoylation of the mevalonate pathway enzyme HMGS-1 regulates metabolism during aging
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1414748111
  contributor:
    fullname: Sapir
– volume: 21
  start-page: 1655
  year: 2010
  ident: ref_16
  article-title: Influence of Fe(II) and Fe(III) on the expression of genes related to cholesterol- and fatty acid metabolism in human vascular smooth muscle cells
  publication-title: J. Mater. Sci. Mater. Med.
  doi: 10.1007/s10856-010-4014-8
  contributor:
    fullname: Drynda
– volume: 368
  start-page: 576
  year: 2013
  ident: ref_8
  article-title: Statin use and reduced cancer-related mortality
  publication-title: N. Engl. J. Med.
  contributor:
    fullname: Nielsen
– volume: 74
  start-page: 4772
  year: 2014
  ident: ref_13
  article-title: Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-14-0130
  contributor:
    fullname: Pandyra
– volume: 51
  start-page: 939
  year: 2012
  ident: ref_46
  article-title: Notch2-induced COX-2 expression enhancing gastric cancer progression
  publication-title: Mol. Carcinog.
  doi: 10.1002/mc.20865
  contributor:
    fullname: Tseng
– volume: 107
  start-page: 15051
  year: 2010
  ident: ref_3
  article-title: Dysregulation of the mevalonate pathway promotes transformation
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.0910258107
  contributor:
    fullname: Clendening
– volume: 17
  start-page: 1374
  year: 2016
  ident: ref_26
  article-title: The integrated stress response
  publication-title: EMBO Rep.
  doi: 10.15252/embr.201642195
  contributor:
    fullname: Koryga
– volume: 11
  start-page: 1578
  year: 2012
  ident: ref_39
  article-title: Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues
  publication-title: Mol. Cell Proteom.
  doi: 10.1074/mcp.M112.017905
  contributor:
    fullname: Wagner
– volume: 136
  start-page: E359
  year: 2015
  ident: ref_1
  article-title: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012
  publication-title: Int. J. Cancer.
  doi: 10.1002/ijc.29210
  contributor:
    fullname: Ferlay
– volume: 122
  start-page: 4621
  year: 2012
  ident: ref_31
  article-title: ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth
  publication-title: J. Clin. Investig.
  doi: 10.1172/JCI62973
  contributor:
    fullname: Hart
– volume: 8
  start-page: 1053
  year: 2006
  ident: ref_32
  article-title: Anti-oncogenic role of the endoplasmic reticulum differentially activated by mutations in the MAPK pathway
  publication-title: Nat. Cell Biol.
  doi: 10.1038/ncb1471
  contributor:
    fullname: Denoyelle
– volume: 21
  start-page: 889
  year: 2019
  ident: ref_33
  article-title: ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression
  publication-title: Nat. Cell Biol.
  doi: 10.1038/s41556-019-0347-9
  contributor:
    fullname: Tameire
– volume: 211
  start-page: 29
  year: 2012
  ident: ref_34
  article-title: Pharmacologic ER stress induces non-alcoholic steatohepatitis in an animal model
  publication-title: Toxicol. Lett.
  doi: 10.1016/j.toxlet.2012.02.017
  contributor:
    fullname: Lee
– volume: 44
  start-page: 325
  year: 2011
  ident: ref_37
  article-title: Systematic and quantitative assessment of the ubiquitin-modified proteome
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2011.08.025
  contributor:
    fullname: Kim
– volume: 288
  start-page: 18707
  year: 2013
  ident: ref_6
  article-title: Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.R113.479808
  contributor:
    fullname: Sharpe
– volume: 1873
  start-page: 188351
  year: 2020
  ident: ref_10
  article-title: Cholesterol and beyond- The role of the mevalonate pathway in cancer biology
  publication-title: Biochim. Biophys. Acta Rev. Cancer
  doi: 10.1016/j.bbcan.2020.188351
  contributor:
    fullname: Gobel
– volume: 3
  start-page: 635
  year: 2011
  ident: ref_40
  article-title: SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2
  publication-title: Aging (Albany NY)
  doi: 10.18632/aging.100339
  contributor:
    fullname: Hirschey
– volume: 115
  start-page: 4787
  year: 2010
  ident: ref_11
  article-title: Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma
  publication-title: Blood
  doi: 10.1182/blood-2009-07-230508
  contributor:
    fullname: Clendening
– ident: ref_20
  doi: 10.1371/journal.pone.0148818
– volume: 19
  start-page: 135
  year: 2020
  ident: ref_14
  article-title: Dipyridamole enhances the cytotoxicities of trametinib against colon cancer cells through combined targeting of HMGCS1 and MEK pathway
  publication-title: Mol. Cancer Ther.
  doi: 10.1158/1535-7163.MCT-19-0413
  contributor:
    fullname: Zhou
– volume: 6
  start-page: 26909
  year: 2015
  ident: ref_19
  article-title: Genome-wide RNAi analysis reveals that simultaneous inhibition of specific mevalonate pathway genes potentiates tumor cell death
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.4817
  contributor:
    fullname: Pandyra
– volume: 339
  start-page: 819
  year: 2013
  ident: ref_21
  article-title: Multiplex genome engineering using CRISPR/Cas systems
  publication-title: Science
  doi: 10.1126/science.1231143
  contributor:
    fullname: Cong
– volume: 28
  start-page: 4829
  year: 2008
  ident: ref_45
  article-title: The activated Notch1 receptor cooperates with alpha-enolase and MBP-1 in modulating c-myc activity
  publication-title: Mol. Cell. Biol.
  doi: 10.1128/MCB.00175-08
  contributor:
    fullname: Hsu
– volume: 15
  start-page: 481
  year: 2013
  ident: ref_30
  article-title: ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death
  publication-title: Nat. Cell Biol.
  doi: 10.1038/ncb2738
  contributor:
    fullname: Han
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Snippet The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This...
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StartPage 1088
SubjectTerms gastric cancer progression
HMGCS1
integrated stress response
mevalonate pathway
pluripotency
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Title Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression
URI https://www.ncbi.nlm.nih.gov/pubmed/32349352
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https://pubmed.ncbi.nlm.nih.gov/PMC7281414
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