MYC-driven inhibition of the glutamate-cysteine ligase promotes glutathione depletion in liver cancer

EMBO Reports

Volumn 18, Issue 4, 2017, Pages 569-585

  Anderton, Brittany ^a,b   Camarda, Roman ^a,b   Balakrishnan, Sanjeev ^a,b   Balakrishnan, Asha ^a,b,c   Kohnz, Rebecca A ^d   Lim, Lionel ^a,b   Evason, Kimberley J ^e   Momcilovic, Olga ^a,b   Kruttwig, Klaus ^a,b   Huang, Qiang ^f   Xu, Guowang ^f   Nomura, Daniel K ^d   Goga, Andrei ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c HANNOVER MEDICAL SCHOOL   (Germany)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^f DALIAN INSTITUTE OF CHEMICAL PHYSICS   (China)

Author keywords

cancer; glutathione; metabolism; miRNA; MYC

Indexed keywords

ABC TRANSPORTER; GLUTAMATE CYSTEINE LIGASE; GLUTAMINE; GLUTATHIONE; GLUTATHIONE DISULFIDE; GLYCINE; MICRORNA; MICRORNA 18A; MINERAL; MYC PROTEIN; SERINE; THREONINE; UNCLASSIFIED DRUG; GCLC PROTEIN, HUMAN; MIRN18 MICRORNA, HUMAN;

ACUTE STRESS; AMINO ACID METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CANCER TISSUE; CONTROLLED STUDY; GLUTATHIONE METABOLISM; HUMAN; IN VIVO STUDY; LIVER CANCER; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PRIMARY TUMOR; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; ANIMAL; ANTAGONISTS AND INHIBITORS; CLUSTER ANALYSIS; DISEASE MODEL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; LIVER TUMOR; METABOLISM; METABOLOME; METABOLOMICS; PROCEDURES; RNA INTERFERENCE; TRANSGENIC MOUSE; TUMOR CELL LINE;

ANIMALS; CELL LINE, TUMOR; CLUSTER ANALYSIS; DISEASE MODELS, ANIMAL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUTAMATE-CYSTEINE LIGASE; GLUTAMINE; GLUTATHIONE; HUMANS; LIVER NEOPLASMS; METABOLIC NETWORKS AND PATHWAYS; METABOLOME; METABOLOMICS; MICE; MICE, TRANSGENIC; MICRORNAS; OXIDATIVE STRESS; PROTO-ONCOGENE PROTEINS C-MYC; RNA INTERFERENCE;

EID: 85013478389     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.15252/embr.201643068     Document Type: Article

References (62)

1. Dang CV (2012) MYC on the path to cancer. Cell 149: 22–35
2. Horiuchi D, Anderton B, Goga A (2014) Taking on challenging targets: making MYC druggable. Am Soc Clin Oncol Educ Book 34: e497–e502
3. Dang CV (2013) MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harb Perspect Med 3: a014217
4. Li B, Simon MC (2013) Molecular pathways: targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer. Clin Cancer Res 19: 5835–5841
5. Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA, Dang CV (2000) Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem 275: 21797–21800
6. Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL, Dang CV (2010) Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci USA 107: 2037–2042
7. David CJ, Chen M, Assanah M, Canoll P, Manley JL (2010) HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 463: 364–368
8. Heiden Vander MG, Lunt SY, Dayton TL, Fiske BP, Israelsen WJ, Mattaini KR, Vokes NI, Stephanopoulos G, Cantley LC, Metallo CM et al (2011) Metabolic pathway alterations that support: cell proliferation. Cold Spring Harb Symp Quant Biol 76: 325–334
9. Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y (2007) Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol 178: 93–105
10. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang X-Y, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB et al (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 105: 18782–18787
11. Yuneva MO, Fan TWM, Allen TD, Higashi RM, Ferraris DV, Tsukamoto T, Matés JM, Alonso FJ, Wang C, Seo Y et al (2012) The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab 15: 157–170
12. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H et al (2012) Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in b cells. Cell Metab 15: 110–121
13. Bott AJ, Peng IC, Fan Y, Faubert B, Zhao L, Li J, Neidler S, Sun Y, Jaber N, Krokowski D et al (2015) Oncogenic MYC induces expression of glutamine synthetase through promoter demethylation. Cell Metab 22: 1068–1077
14. Gao P, Tchernyshyov I, Chang T-C, Lee Y-S, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT et al (2009) c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458: 762–765
15. Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ, Hsieh AL, Gouw AM, Thomas AG, Gao P et al (2015) Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest 125: 2293–2306
16. Kaposi-Novak P, Libbrecht L, Woo HG, Lee YH, Sears NC, Conner EA, Factor VM, Roskams T, Thorgeirsson SS (2009) Central role of c-Myc during malignant conversion in human hepatocarcinogenesis. Cancer Res 69: 2775–2782
17. Sanyal AJ, Yoon SK, Lencioni R (2010) The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist 15(Suppl 4): 14–22
18. Schlaeger C, Longerich T, Schiller C, Bewerunge P, Mehrabi A, Toedt G, Kleeff J, Ehemann V, Eils R, Lichter P et al (2008) Etiology-dependent molecular mechanisms in human hepatocarcinogenesis. Hepatology 47: 511–520
19. Lin CP, Liu CR, Lee CN, Chan TS, Liu HE (2010) Targeting c-Myc as a novel approach for hepatocellular carcinoma. World J Hepatol 2: 16–20
20. Kawate S, Fukusato T, Ohwada S, Watanuki A, Morishita Y (1999) Amplification of c-myc in hepatocellular carcinoma: correlation with clinicopathologic features, proliferative activity and p53 overexpression. Oncology 57: 157–163
21. Peng SY, Lai PL, Hsu HC (1993) Amplification of the c-myc gene in human hepatocellular carcinoma: biologic significance. J Formos Med Assoc 92: 866–870
22. Shachaf CM, Kopelman AM, Arvanitis C, Karlsson A, Beer S, Mandl S, Bachmann MH, Borowsky AD, Ruebner B, Cardiff RD et al (2004) MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431: 1112–1117
23. Hu S, Balakrishnan A, Bok RA, Anderton B, Larson PEZ, Nelson SJ, Kurhanewicz J, Vigneron DB, Goga A (2011) 13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression. Cell Metab 14: 131–142
24. Lim L, Balakrishnan A, Huskey N, Jones KD, Jodari M, Ng R, Song G, Riordan J, Anderton B, Cheung ST et al (2014) MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer. Hepatology 59: 202–215
25. Tanabe M, Kanehisa M (2012) Using the KEGG database resource. Curr Protoc Bioinformatics 38: 1.12.1–1.12.43
26. Wu G, Fang Y-Z, Yang S, Lupton JR, Turner ND (2004) Glutathione metabolism and its implications for health. J Nutr 134: 489–492
27. Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830: 3143–3153
28. Tward AD, Jones KD, Yant S, Kay MA, Wang R, Bishop JM (2005) Genomic progression in mouse models for liver tumors. Cold Spring Harb Symp Quant Biol 70: 217–224
29. Cao Z, Fan-Minogue H, Bellovin DI, Yevtodiyenko A, Arzeno J, Yang Q, Gambhir SS, Felsher DW (2011) MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma are regulated by HMG-CoA reductase. Cancer Res 71: 2286–2297
30. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ et al (2005) A microRNA polycistron as a potential human oncogene. Nature 435: 828–833
31. Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT et al (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 38: 1060–1065
32. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435: 839–843
33. Guil S, Cáceres JF (2007) The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nat Struct Mol Biol 14: 591–596
34. Liu WH, Yeh SH, Lu CC, Yu SL, Chen HY, Lin CY, Chen DS, Chen PJ (2009) MicroRNA-18a prevents estrogen receptor-α expression, promoting proliferation of hepatocellular carcinoma cells. Gastroenterology 136: 683–693
35. Li L, Guo Z, Wang J, Mao Y, Gao Q (2012) Serum miR-18a: a potential marker for hepatitis B virus-related hepatocellular carcinoma screening. Dig Dis Sci 57: 2910–2916
36. Burchard J, Zhang C, Liu AM, Poon RTP, Lee NPY, Wong K-F, Sham PC, Lam BY, Ferguson MD, Tokiwa G et al (2010) microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma. Mol Syst Biol 6: 402
37. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40: 499–507
38. Pedica F, Ruzzenente A, Bagante F, Capelli P, Cataldo I, Pedron S, Iacono C, Chilosi M, Scarpa A, Brunelli M et al (2013) A re-emerging marker for prognosis in hepatocellular carcinoma: the add-value of FISHing c-myc gene for early relapse. PLoS One 8: e68206
39. Huang Q, Tan Y, Yin P, Ye G, Gao P, Lu X, Wang H, Xu G (2013) Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics. Cancer Res 73: 4992–5002
40. Budhu A, Roessler S, Zhao X, Yu Z, Forgues M, Ji J, Karoly E, Qin LX, Ye QH, Jia HL et al (2013) Integrated metabolite and gene expression profiles identify lipid biomarkers associated with progression of hepatocellular carcinoma and patient outcomes. Gastroenterology 144: 1066–1075
41. Fussell KC, Udasin RG, Gray JP, Mishin V, Smith PJS, Heck DE, Laskin JD (2011) Redox cycling and increased oxygen utilization contribute to diquat-induced oxidative stress and cytotoxicity in Chinese hamster ovary cells overexpressing NADPH-cytochrome P450 reductase. Free Radic Biol Med 50: 874–882
42. Han E-S, Muller FL, Pérez VI, Qi W, Liang H, Xi L, Fu C, Doyle E, Hickey M, Cornell J et al (2008) The in vivo gene expression signature of oxidative stress. Physiol Genomics 34: 112–126
43. + hematopoietic progenitor cells. Mol Cancer Res 9: 1054–1066
44. Nikiforov MA, Chandriani S, O'Connell B, Petrenko O, Kotenko I, Beavis A, Sedivy JM, Cole MD (2002) A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism. Mol Cell Biol 22: 5793–5800
45. Kress TR, Pellanda P, Pellegrinet L, Bianchi V, Nicoli P, Doni M, Recordati C, Bianchi S, Rotta L, Capra T et al (2016) Identification of Myc-dependent transcriptional programs in oncogene-addicted liver tumors. Cancer Res 76: 3463–3472
46. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 104: 19345–19350
47. Levy S, Forman HJ (2010) c-Myc is a Nrf2-interacting protein that negatively regulates phase II genes through their electrophile responsive elements. IUBMB Life 62: 237–246
48. Benassi B, Fanciulli M, Fiorentino F, Porrello A, Chiorino G, Loda M, Zupi G, Biroccio A (2006) c-Myc phosphorylation is required for cellular response to oxidative stress. Mol Cell 21: 509–519
49. Hinchman CA, Ballatori N (1994) Glutathione conjugation and conversion to mercapturic acids can occur as an intrahepatic process. J Toxicol Environ Health 41: 387–409
50. Arnér ESJ, Holmgren A (2006) The thioredoxin system in cancer. Semin Cancer Biol 16: 420–426
51. Singh A, Bodas M, Wakabayashi N, Bunz F, Biswal S (2010) Gain of Nrf2 function in non-small-cell lung cancer cells confers radioresistance. Antioxid Redox Signal 13: 1627–1637
52. Shibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, Tsuta K, Asamura H, Yamamoto M, Hirohashi S (2008) Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci USA 105: 13568–13573
53. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010) Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160: 1577–1579
54. Adams SB, Setton LA, Kensicki E, Bolognesi MP, Toth AP, Nettles DL (2012) Global metabolic profiling of human osteoarthritic synovium. Osteoarthr Cartil 20: 64–67
55. Chen X, Xie C, Sun L, Ding J, Cai H (2015) Longitudinal metabolomics profiling of Parkinson's disease-related α-synuclein A53T transgenic mice. PLoS One 10: e0136612
56. Chen Y, Tang Y, Zhang YC, Huang XH, Xie YQ, Xiang Y (2015) A metabolomic study of rats with doxorubicin-induced cardiomyopathy and Shengmai injection treatment. PLoS One 10: e0125209
57. Benjamin DI, Louie SM, Mulvihill MM, Kohnz RA, Li DS, Chan LG, Sorrentino A, Bandyopadhyay S, Cozzo A, Ohiri A et al (2014) Inositol phosphate recycling regulates glycolytic and lipid metabolism that drives cancer aggressiveness. ACS Chem Biol 9: 1340–1350
58. Smyth G (2005) limma: Linear models for microarray data. In Bioinformatics and computational biology solutions using R and bioconductor, Gentleman R, Carey VJ, Huber W, Irizarry RA, Dudoit S (eds), pp 397–420. New York: Springer.
59. Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD (2012) The SVA package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28: 882–883
60. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43: e47
61. Blake JA, Bult CJ, Eppig JT, Kadin JA, Richardson JE (2014) The Mouse Genome Database: integration of and access to knowledge about the laboratory mouse. Nucleic Acids Res 42: D810–D817
62. Hastie T, Tibshirani R, Sherlock G (1999) Imputing missing data for gene expression arrays. http://ww.web.stanford.edu/~hastie/Papers/missing.pdf