Pyruvate kinase M2: Multiple faces for conferring benefits on cancer cells

Clinical Cancer Research

Volumn 18, Issue 20, 2012, Pages 5554-5561

  Tamada, Mayumi ^a   Suematsu, Makoto ^a,b   Saya, Hideyuki ^a,b  

^a KEIO UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CYCLIN D1; HERMES ANTIGEN; ISOENZYME; MUCIN 1; MYC PROTEIN; PHOSPHOTRANSFERASE; PYRUVATE KINASE; PYRUVATE KINASE M1; PYRUVATE KINASE M2; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR;

CANCER CELL; CANCER GROWTH; DOWN REGULATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME LOCALIZATION; GLYCOLYSIS; HUMAN; MOLECULAR INTERACTION; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; REVIEW; UPREGULATION;

ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; ENZYME INHIBITORS; GLYCOLYSIS; HUMANS; METABOLIC NETWORKS AND PATHWAYS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PHOSPHORYLATION; PYRUVATE KINASE;

EID: 84867559423     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-12-0859     Document Type: Review

References (86)

1. Warburg O, Wind F, Negelein E. The metabolismof tumors in the body. J Gen Physiol 1927;8:519-30.
2. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev 2004;4:891-9. (Pubitemid 39472955)
3. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008;452:230-3. (Pubitemid 351380249)
4. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029-33.
5. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 2008;452:181-6. (Pubitemid 351380242)
6. Hitosugi T, Kang S, Vander Heiden MG, Chung TW, Elf S, Lythgoe K, et al. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal 2009;2:ra73.
7. Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG, Krainer AR. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci U S A 2010;107:1894-9.
8. Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol 2011;43:969-80.
9. Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 2005;15:300-8. (Pubitemid 41058775)
10. Noguchi T, Yamada K, Inoue H, Matsuda T, Tanaka T. The L- and Rtype isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters. J Biol Chem 1987;262:14366-71.
11. David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 2010;463:364-8.
12. Noguchi T, Inoue H, Tanaka T. The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing. J Biol Chem 1986;261:13807-12. (Pubitemid 17196407)
13. 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;2:393-400.
14. Lee J, Kim HK, Han YM, Kim J. Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription. Int J Biochem Cell Biol 2008;40:1043-54.
15. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev 2011;11:85-95.
16. Chen M, David CJ, Manley JL. Concentration-dependent control of pyruvate kinaseMmutually exclusive splicing by hnRNP proteins. Nat Struct Mol Biol 2012;19:346-54.
17. Goldberg MS, Sharp PA. Pyruvate kinase M2-speci fic siRNA induces apoptosis and tumor regression. J Exp Med 2012;209:217-24.
18. Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 2011;334:1278-83.
19. Hoshino A, Hirst JA, Fujii H. Regulation of cell proliferation by interleukin-3-induced nuclear translocation of pyruvate kinase. J Biol Chem 2007;282:17706-11. (Pubitemid 47100326)
20. Gao X, Wang H, Yang JJ, Liu X, Liu ZR. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol Cell 2012;45: 598-609.
21. Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 2011;145:732-44.
22. Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, et al. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell 2011;42:719-30.
23. Panasyuk G, Espeillac C, Chauvin C, Pradelli LA, Horie Y, Suzuki A, et al. PPARgamma contributes to PKM2 and HK2 expression in fatty liver. Nat Commun 2012;3:672.
24. Sun Q, Chen X,MaJ, Peng H,WangF, Zha X, et al. Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad SciUS A 2011;108:4129-34.
25. Luftner D, Mesterharm J, Akrivakis C, Geppert R, Petrides PE, Wernecke KD, et al. Tumor type M2 pyruvate kinase expression in advanced breast cancer. Anticancer Res 2000;20:5077-82. (Pubitemid 32319084)
26. Schneider J, Neu K, Grimm H, Velcovsky HG, Weisse G, Eigenbrodt E. Tumor M2-pyruvate kinase in lung cancer patients: immunohistochemical detection and disease monitoring. Anticancer Res 2002;22:311-8. (Pubitemid 34475318)
27. Cerwenka H, Aigner R, Bacher H, Werkgartner G, el-Shabrawi A, Quehenberger F, et al. TUM2-PK (pyruvate kinase type tumor M2), CA19-9 and CEA in patients with benign, malignant and metastasizing pancreatic lesions. Anticancer Res 1999;19:849-51. (Pubitemid 29168343)
28. Wittwer JA, Robbins D, Wang F, Codarin S, Shen X, Kevil CG, et al. Enhancing mitochondrial respiration suppresses tumor promoter TPA-induced PKM2 expression and cell transformation in skin epidermal JB6 cells. Cancer Prevent Res 2011;4:1476-84.
29. Pfeiffer T, Schuster S, Bonhoeffer S. Cooperation and competition in the evolution of ATP-producing pathways. Science 2001;292:504-7. (Pubitemid 32335953)
30. Hamanaka RB, Chandel NS. Targeting glucose metabolism for cancer therapy. J Exp Med 2012;209:211-5.
31. Vazquez A, Liu J, Zhou Y, Oltvai ZN. Catabolic efficiency of aerobic glycolysis: the Warburg effect revisited. BMC Syst Biol 2010;4:58.
32. Jiang JK, Boxer MB, Vander Heiden MG, Shen M, Skoumbourdis AP, Southall N, et al. Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg Med Chem Lett 2010;20:3387-93.
33. Boxer MB, Jiang JK, Vander Heiden MG, Shen M, Skoumbourdis AP, Southall N, et al. Evaluation of substituted N,N′-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J Med Chem 2010;53:1048-55.
34. Dang CV. PKM2 tyrosine phosphorylation and glutamine metabolism signal a different view of the Warburg effect. Sci Signal 2009;2:pe75.
35. Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 2010;329:1492-9.
36. Wu X, Zhou Y, Zhang K, Liu Q, Guo D. Isoform-specific interaction of pyruvate kinase with hepatitis C virus NS5B. FEBS Lett 2008;582:2155-60.
37. Shimada N, Shinagawa T, Ishii S. Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein. Gens Cells 2008;13:245-54. (Pubitemid 351292280)
38. Mazurek S, Drexler HC, Troppmair J, Eigenbrodt E, Rapp UR. Regulation of pyruvate kinase typeM2 byA-Raf: a possible glycolytic stop or go mechanism. Anticancer Res 2007;27:3963-71.
39. Siwko S, Mochly-Rosen D. Use of a novel method to find substrates of protein kinase Cdelta identifiesM2 pyruvate kinase. Int J Biochem Cell Biol 2007;39:978-87. (Pubitemid 46575328)
40. LeMellay V, Houben R, Troppmair J, Hagemann C, Mazurek S, Frey U, et al. Regulation of glycolysis by Raf protein serine/threonine kinases. Adv Enzyme Regul 2002;42:317-32. (Pubitemid 35033546)
41. Zwerschke W, Mazurek S, Massimi P, Banks L, Eigenbrodt E, Jansen-Durr P. Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci U S A 1999;96:1291-6. (Pubitemid 29098444)
42. Presek P, Glossmann H, Eigenbrodt E, Schoner W, Rubsamen H, Friis RR, et al. Similarities between a phosphoprotein (pp60src)-associated protein kinase of Rous sarcoma virus and a cyclic adenosine 30 :50- monophosphate-independent protein kinase that phosphorylates pyruvate kinase type M2. Cancer Res 1980;40:1733-41. (Pubitemid 10102025)
43. Ryu H, Walker JK, KimS, Koo N, Barak LS, Noguchi T, et al. Regulation of M2-type pyruvate kinase mediated by the high-af finity IgE receptors is required for mast cell degranulation. Br J Pharmacol 2008;154:1035-46. (Pubitemid 351915052)
44. Zhang Z, Liu Q, Che Y, Yuan X, Dai L, Zeng B, et al. Antigen presentation by dendritic cells in tumors is disrupted by altered metabolism that involves pyruvate kinase M2 and its interaction with SOCS3. Cancer Res 2010;70:89-98.
45. Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 2012;21:297-308.
46. Ashizawa K, Willingham MC, Liang CM, Cheng SY. In vivo regulation of monomer-tetramer conversion of pyruvate kinase subtype M2 by glucose is mediated via fructose 1,6-bisphosphate. J Biol Chem 1991;266:16842-6. (Pubitemid 21907876)
47. Eigenbrodt E, Leib S, Kramer W, Friis RR, Schoner W. Structural and kinetic differences between the M2 type pyruvate kinases from lung and various tumors. Biomed Biochim Acta 1983;42:S278-82. (Pubitemid 14130569)
48. Ye J, Mancuso A, Tong X, Ward PS, Fan J, Rabinowitz JD, et al. Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc Natl Acad Sci U S A 2012;109:6904-9.
49. Mazurek S, Grimm H, Boschek CB, Vaupel P, Eigenbrodt E. Pyruvate kinase type M2: a crossroad in the tumor metabolome. Br J Nutr 2002;87 Suppl 1:S23-9. (Pubitemid 34134101)
50. Kosugi M, Ahmad R, Alam M, Uchida Y, Kufe D. MUC1-C oncoprotein regulates glycolysis and pyruvate kinase M2 activity in cancer cells. PLoS One 2011;6:e28234.
51. Tamada M, Nagano O, Tateyama S, Ohmura M, Yae T, Ishimoto T, et al. Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells. Cancer Res 2012;72:1438-48.
52. Yang W, Xia Y, Ji H, Zheng Y, Liang J, Huang W, et al. Nuclear PKM2 regulates beta-catenin transactivation upon EGFR activation. Nature 2011;480:118-22.
53. Diaz-Jullien C, Moreira D, Sarandeses CS, Covelo G, Barbeito P, Freire M. The M2-type isoenzyme of pyruvate kinase phosphorylates prothymosin alpha in proliferating lymphocytes. Biochim Biophys Acta 2011;1814:355-65.
54. Gupta V, Bamezai RN. Human pyruvate kinase M2: a multifunctional protein. Protein Sci 2010;19:2031-44.
55. Spoden GA, Morandell D, Ehehalt D, Fiedler M, Jansen-Durr P, Hermann M, et al. The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2. J Cell Biochem 2009;107:293-302.
56. Spoden GA, Mazurek S, Morandell D, Bacher N, Ausserlechner MJ, Jansen-Durr P, et al. Isotype-specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation. Int J Cancer 2008;123:312-21. (Pubitemid 351842015)
57. Duan HF, Hu XW, Chen JL, Gao LH, Xi YY, Lu Y, et al. Antitumor activities of TEM8-Fc: an engineered antibody-like molecule targeting tumor endothelial marker 8. J Natl Cancer Inst 2007;99:1551-5. (Pubitemid 351767233)
58. Stetak A, Veress R, Ovadi J, Csermely P, Keri G, Ullrich A. Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Res 2007;67:1602-8. (Pubitemid 46383385)
59. Li Y, Chang Y, Zhang L, Feng Q, Liu Z, Zhang Y, et al. High glucose upregulates pantothenate kinase 4 (PanK4) and thus affects M2-type pyruvate kinase (Pkm2). Mol Cell Biochem 2005;277:117-25. (Pubitemid 41236193)
60. Garcia-Gonzalo FR, Cruz C, Munoz P, Mazurek S, Eigenbrodt E, Ventura F, et al. Interaction between HERC1 and M2-type pyruvate kinase. FEBS Lett 2003;539:78-84. (Pubitemid 36351291)
61. Ignacak J, Stachurska MB. The dual activity of pyruvate kinase typeM2 from chromatin extracts of neoplastic cells. Comp Biochem Physiol B Biochem Mol Biol 2003;134:425-33. (Pubitemid 36293749)
62. Mazurek S, Zwerschke W, Jansen-Durr P, Eigenbrodt E. Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and glutaminolysis: role of pyruvate kinase type M2 and the glycolytic-enzyme complex. Biochem J 2001;356:247-56. (Pubitemid 34275727)
63. Oak MH, Cheong H, Kim KM. Activation of Fc epsilon RI inhibits the pyruvate kinase through direct interaction with the gamma-chain. Int Arch Allergy Immunol 1999;119:95-100. (Pubitemid 29304464)
64. Williams JM, Chen GC, Zhu L, Rest RF. Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth. Mol Microbiol 1998;27:171-86. (Pubitemid 28022586)
65. Kato H, Fukuda T, Parkison C, McPhie P, Cheng SY. Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase. Proc Natl Acad Sci U S A 1989;86:7861-5. (Pubitemid 19265286)
66. Munoz-Pinedo C, El Mjiyad N, Ricci JE. Cancer metabolism: current perspectives and future directions. Cell Death Dis 2012;3:e248.
67. Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clinical Cancer Res 2009;15:6479-83.
68. Nagano O, Saya H. Mechanism and biological significance of CD44 cleavage. Cancer Sci 2004;95:930-5. (Pubitemid 40089583)
69. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev 2008;8:755-68.
70. Gruning NM, Ralser M. Cancer: sacrifice for survival. Nature 2011;480:190-1.
71. Hamanaka RB, Chandel NS. Cell biology. Warburg effect and redox balance. Science 2011;334:1219-20.
72. Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer cell 2011;19:387-400.
73. Meijer TWH, Kaanders JHAM, Span PN, Bussink J. Targeting hypoxia, HIF-1 and tumor glucose metabolismto improve radiotherapy efficacy. Clin Cancer Res 2012;18:5585-94.
74. Jerby L, Ruppin E. Predicting drug targets and biomarkers of cancer via genome-scale metabolic modeling. Clin Cancer Res 2012;18: 5572-84.
75. Dang CV, Hamaker M, Sun P, Le A, Gao P. Therapeutic targeting of cancer cell metabolism. J Mol Med 2011;89:205-12.
76. Iaccarino I, Martins LM. Therapeutic targets in cancer cell metabolism and death. Cell Death Differ 2011;18:565-70.
77. VanderHeiden MG. Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov 2011;10:671-84.
78. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 2007;11:37-51. (Pubitemid 46054520)
79. Spoden GA, Rostek U, Lechner S, Mitterberger M, Mazurek S, Zwerschke W. Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply. Exp Cell Res 2009;315:2765-74.
80. Guo W, Zhang Y, Chen T, Wang Y, Xue J, Zhang Y, et al. Efficacy of RNAi targeting of pyruvate kinaseM2 combined with cisplatin in a lung cancer model. J Cancer Res Clin Oncol 2011;137:65-72.
81. Walsh MJ, Brimacombe KR, Veith H, Bougie JM, Daniel T, Leister W, et al. 2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg Med Chem Lett 2011;21:6322-7.
82. Hathurusinghe HR, Goonetilleke KS, Siriwardena AK. Current status of tumor M2 pyruvate kinase (tumor M2-PK) as a biomarker of gastrointestinal malignancy. Ann Surg Oncol 2007;14:2714-20. (Pubitemid 47460645)
83. Yang H, Ye D, Guan K-L, Xiong Y. IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res 2012;18:5562-71.
84. Macintyre AN, Rathmell JC.PKM2and the tricky balance of growth and energy in cancer. Molecular cell 2011;42:713-4.
85. Tennant DA. PK-M2 makes cells sweeter on HIF1. Cell 2011;145:647-9.
86. Chiavarina B, Whitaker-Menezes D, Martinez-Outschoorn UE, Witkiewicz AK, Birbe RC, Howell A, et al. Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth. Cancer Biol Ther 2011;12:1101-13.