PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis

Journal of Clinical Investigation

Volumn 126, Issue 2, 2016, Pages 681-694

  Nguyen, Alexander ^a   Loo, Jia Min ^a   Mital, Rohit ^a   Weinberg, Ethan M ^a   Man, Fung Ying ^a   Zeng, Zhaoshi ^b   Paty, Philip B ^b   Saltz, Leonard ^b   Janjigian, Yelena Y ^b   De Stanchina, Elisa ^b   Tavazoie, Sohail F ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUTAMATE CYSTEINE LIGASE; GLUTATHIONE; PYRUVATE KINASE; CARRIER PROTEIN; MEMBRANE PROTEIN; THYROID HORMONE; THYROID HORMONE-BINDING PROTEINS; TUMOR PROTEIN;

ARTICLE; CANCER CELL; CANCER SURVIVAL; CARCINOGENESIS; CELL DEATH; CELL DENSITY; CELL HYPOXIA; CELL SURVIVAL; COLORECTAL CANCER; CONTROLLED STUDY; ENZYME ACTIVITY; GLUTATHIONE METABOLISM; GLYCOLYSIS; HUMAN; HUMAN CELL; LIVER METASTASIS; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; ANIMAL; BIOSYNTHESIS; CANCER TRANSPLANTATION; COLORECTAL TUMOR; ENZYMOLOGY; GENETICS; LIVER TUMOR; METABOLISM; METASTASIS; MOUSE; NONOBESE DIABETIC MOUSE; PATHOLOGY; SCID MOUSE; SECONDARY; TUMOR CELL LINE; XENOGRAFT;

ANIMALS; CARRIER PROTEINS; CELL LINE, TUMOR; COLORECTAL NEOPLASMS; GLUTATHIONE; HETEROGRAFTS; HUMANS; LIVER NEOPLASMS; MEMBRANE PROTEINS; MICE; MICE, INBRED NOD; MICE, SCID; NEOPLASM METASTASIS; NEOPLASM PROTEINS; NEOPLASM TRANSPLANTATION; PYRUVATE KINASE; THYROID HORMONES;

EID: 84956961637     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI83587     Document Type: Article

References (55)

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9-29.
2. Ferlay J, et al. Cancer incidence mortality worldwide: Sources, methods major patterns in GLOBOCAN 2012. Int J Cancer. 2014;136(5):E359-E386.
3. Davies JM, Goldberg RM. Treatment of metastatic colorectal cancer. Semin Oncol. 2011;38(4):552-560.
4. Talmadge JE, Fidler IJ. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 2010;70(14):5649-5669.
5. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell. 2006;127(4):679-695.
6. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
7. Luzzi KJ, et al. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol. 1998;153(3):865-873.
8. Jungermann K, Kietzmann T. Zonation of parenchymal and nonparenchymal metabolism in liver. Annu Rev Nutr. 1996;16:179-203.
9. Sullivan WJ, Christofk HR. The metabolic milieu of metastases. Cell. 2015;160(3):363-364.
10. Beronja S, et al. RNAi screens in mice identify physiological regulators of oncogenic growth. Nature. 2013;501(7466):185-190.
11. Anastasiou D, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science. 2011;334(6060):1278-1283.
12. Root DE, Hacohen N, Hahn WC, Lander ES, Sabatini DM. Genome-scale loss-of-function screening with a lentiviral RNAi library. Nat Methods. 2006;3(9):715-719.
13. Loo JM, et al. Extracellular metabolic energetics can promote cancer progression. Cell. 2015;160(3):393-406.
14. Kaelin WG Jr. Molecular biology. Use and abuse of RNAi to study mammalian gene function. Science. 2012;337(6093):421-422.
15. Luo B, et al. Highly parallel identification of essential genes in cancer cells. Proc Natl Acad Sci U S A. 2008;105(51):20380-20385.
16. Reinmuth N, et al. Impact of insulin-like growth factor receptor-I function on angiogenesis, growth, and metastasis of colon cancer. Lab Invest. 2002;82(10):1377-1389.
17. Badiola I, Villace P, Basaldua I, Olaso E. Downregulation of discoidin domain receptor 2 in A375 human melanoma cells reduces its experimental liver metastasis ability. Oncol Rep. 2011;26(4):971-978.
18. Luo W, Semenza GL. Emerging roles of PKM2 in cell metabolism and cancer progression. Trends Endocrinol Metab. 2012;23(11):560-566.
19. Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol. 2005;15(4):300-308.
20. Imamura K, Tanaka T. Multimolecular forms of pyruvate kinase from rat and other mammalian tissues. I. Electrophoretic studies. J Biochem. 1972;71(6):1043-1051.
21. Osterman J, Fritz PJ. Pyruvate kinase isozymes from rat intestinal mucosa. Characterization and the effect of fasting and refeeding. Biochemistry. 1974;13(8):1731-1736.
22. Domingo M, Einig C, Eigenbrodt E, Reinacher M. Immunohistological demonstration of pyruvate kinase isoenzyme type L in rat with monoclonal antibodies. J Histochem Cytochem. 1992;40(5):665-673.
23. Uhlen M, et al. Towards a knowledge-based Human Protein Atlas. Nat Biotechnol. 2010;28(12):1248-1250.
24. Ki DH, et al. Whole genome analysis for liver metastasis gene signatures in colorectal cancer. Int J Cancer. 2007;121(9):2005-2012.
25. Sheffer M, et al. Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer. Proc Natl Acad Sci U S A. 2009;106(17):7131-7136.
26. Stange DE, et al. Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain. Gut. 2010;59(9):1236-1244.
27. Kim SK, et al. A nineteen gene-based risk score classifier predicts prognosis of colorectal cancer patients. Mol Oncol. 2014;8(8):1653-1666.
28. Watanabe T, et al. Gene expression signature and response to the use of leucovorin, fluorouracil and oxaliplatin in colorectal cancer patients. Clin Transl Oncol. 2011;13(6):419-425.
29. Matsuyama T, et al. MUC12 mRNA expression is an independent marker of prognosis in stage II and stage III colorectal cancer. Int J Cancer. 2010;127(10):2292-2299.
30. Kikuchi A, et al. Identification of NUCKS1 as a colorectal cancer prognostic marker through integrated expression and copy number analysis. Int J Cancer. 2013;132(10):2295-2302.
31. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423-1437.
32. Bao S, et al. Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. Cancer Cell. 2004;5(4):329-339.
33. Vermeulen PB, et al. Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. J Pathol. 2001;195(3):336-342.
34. Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS. Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell. 1994;76(5):865-873.
35. Bluemlein K, Gruning NM, Feichtinger RG, Lehrach H, Kofler B, Ralser M. No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis. Oncotarget. 2011;2(5):393-400.
36. Christofk HR, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008;452(7184):230-233.
37. Thangaraju M, Carswell KN, Prasad PD, Ganapathy V. Colon cancer cells maintain low levels of pyruvate to avoid cell death caused by inhibition of HDAC1/HDAC3. Biochem J. 2009;417(1):379-389.
38. Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol. 2011;43(7):969-980.
39. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature. 2008;452(7184):181-186.
40. Lunt SY, et al. Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation. Mol Cell. 2015;57(1):95-107.
41. Gerriets VA, et al. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest. 2015;125(1):194-207.
42. Sheta EA, Trout H, Gildea JJ, Harding MA, Theodorescu D. Cell density mediated pericellular hypoxia leads to induction of HIF-1alpha via nitric oxide and Ras/MAP kinase mediated signaling pathways. Oncogene. 2001; 20(52):7624-7634.
43. Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat Rev Cancer. 2008;8(12):967-975.
44. Vander Heiden MG, et al. Identification of small molecule inhibitors of pyruvate kinase M2. Bio chem Pharmacol. 2010;79(8):1118-1124.
45. Griffith OW. Biologic and pharmacologic regulation of mammalian glutathione synthesis. Free Radic Biol Med. 1999;27(9-10):922-935.
46. Schulze A, Harris AL. How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature. 2012;491(7424):364-373.
47. Chaneton B, et al. Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature. 2012;491(7424):458-462.
48. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029-1033.
49. Yamada K, Noguchi T. Nutrient and hormonal regulation of pyruvate kinase gene expression. Biochem J. 1999;337(Pt 1):1-11.
50. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer. 2003;3(6):453-458.
51. Obrador E, Benlloch M, Pellicer JA, Asensi M, Estrela JM. Intertissue flow of glutathione (GSH) as a tumor growth-promoting mechanism: interleukin 6 induces GSH release from hepatocytes in metastatic B16 melanoma-bearing mice. J Biol Chem. 2011;286(18):15716-15727.
52. Harris IS, et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell. 2015;27(2):211-222.
53. Tokutake N, Hiratake J, Katoh M, Irie T, Kato H, Oda J. Design, synthesis and evaluation of transition-state analogue inhibitors of Escherichia coli gamma-glutamylcysteine synthetase. Bioorg Med Chem. 1998;6(10):1935-1953.
54. Anastasiou D, et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol. 2012;8(10):839-847.
55. Watanabe T, et al. A novel model of continuous depletion of glutathione in mice treated with L-buthionine (S,R)-sulfoximine. J Toxicol Sci. 2003;28(5):455-469.