Alternative splicing rewires cellular metabolism to turn on the Warburg effect

Biomedical Research

Volumn 23, Issue SPEC. ISSUE, 2012, Pages 25-30

  Palazzo, Alexander F ^a   Mahadevan, Kohila ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Metabolic switch; mRNA; Oncogenesis; Splicing; Warburg effect

Indexed keywords

ADENOSINE TRIPHOSPHATASE; GLUCOSE; ISOENZYME; MESSENGER RNA; MYC PROTEIN; PHOSPHOENOLPYRUVATE; PHOSPHOGLYCERATE MUTASE; PHOSPHOGLYCERATE MUTASE 1; POLYPYRIMIDINE TRACT BINDING PROTEIN; PYRUVATE KINASE; PYRUVATE KINASE ISOENZYME M 1; PYRUVATE KINASE ISOENZYME M 2; UNCLASSIFIED DRUG;

AEROBIC METABOLISM; ALTERNATIVE RNA SPLICING; CARCINOGENESIS; CELL METABOLISM; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME LOCALIZATION; ENZYME MECHANISM; GLUCOSE TRANSPORT; GLYCOLYSIS; HUMAN; METABOLIC REGULATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PHYSIOLOGICAL PROCESS; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; RNA BINDING; SIGNAL TRANSDUCTION; WARBURG EFFECT;

EID: 84857158310     PISSN: 0970938X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (60)

1. Foulds L. The experimental study of tumor progression: A review. Cancer Res. 1954; 14(5):327-339.
2. Nowell PC. The clonal evolution of tumor cell populations. Science. 1976; 194 (4260): 23-28.
3. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100 (1): 57-70.
4. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646-574.
5. Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011; 11(5): 325-337.
6. Warburg O. Otto Warburg-Nobel Lecture, The oxygen-transferring ferment of respiartion Nobel Lectures. 1931:254-268. Elsevier Publishing Company, Amsterdam, 1965.
7. Bechtel W. Discovering cell mechanisms: The creation of modern cell biology. 2006: 94-115. Cambridge university press.
8. Racker E. History of the Pasteur effect and its pathobiology. Mol Cell Biochem. 1974; 5 (1-2): 17-23.
9. Warburg O. On the origin of cancer cells. Science. 1956; 123 (3191): 309-314.
10. Warburg O. On respiratory impairment in cancer cells. Science. 1956; 124 (3215): 269-270.
11. Warburg O. Ueber den stoffwechsel der tumoren. Constable. 1930.
12. Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011; 27: 441-464.
13. Weber WA, Avril N, Schwaiger M. Relevance of positron emission tomography (PET) in oncology. Strahlenther Onkol. 1999; 175 (8): 356-373.
14. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004; 4(11):891-9.
15. Hawkins RA, Phelps ME. PET in clinical oncology. Cancer Metastasis Rev. 1988; 7 (2):119-142.
16. Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol. 2005; 202 (3): 654-662.
17. Tennant DA, Duran RV, Boulahbel H, Gottlieb E. Metabolic transformation in cancer. Carcinogenesis. 2009; 30 (8): 1269-1280.
18. Altenberg B, Greulich KO. Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics. 2004; 84 (6):1014-20.
19. Mazurek S, Eigenbrodt E. The tumor metabolome. Anticancer Res. 2003; 23 (2A): 1149-1154.
20. Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev. 2001; 15 (11): 1406-1418.
21. Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen JE, Gottlob K, et al. Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell. 2004; 16 (5): 819-830.
22. Yanagawa T, Funasaka T, Tsutsumi S, Watanabe H, Raz A. Novel roles of the autocrine motility factor/- phosphoglucose isomerase in tumor malignancy. Endocr Relat Cancer. 2004; 11(4): 749-759.
23. Atsumi T, Chesney J, Metz C, Leng L, Donnelly S, Makita Z, et al. High expression of inducible 6- phosphofructo-2-kinase/fructose-2,6-bisphosphatase (iPFK-2; PFKFB3) in human cancers. Cancer Res. 2002; 62 (20): 5881-5887.
24. Minchenko A, Leshchinsky I, Opentanova I, Sang N, Srinivas V, Armstead V, et al. Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) gene. Its possible role in the Warburg effect. J Biol Chem. 2002; 277 (8): 6183-6187.
25. 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 (7184): 230-3.
26. Eigenbrodt E, Reinacher M, Scheefers-Borchel U, Scheefers H, Friis R. Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells. Crit Rev Oncog. 1992; 3(1-2): 91-115.
27. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate kinase M2 is a phosphotyrosinebinding protein. Nature. 2008; 452 (7184): 181-186.
28. Presek P, Reinacher M, Eigenbrodt E. Pyruvate kinase type M2 is phosphorylated at tyrosine residues in cells transformed by Rous sarcoma virus. FEBS Lett. 1988; 242 (1): 194-198.
29. 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.
30. 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 (29): 13807-13812.
31. Letunic I, Copley RR, Bork P. Common exon duplication in animals and its role in alternative splicing. Hum Mol Genet. 2002; 11 (13):1561-1567.
32. Hardt PD, Mazurek S, Toepler M, Schlierbach P, Bretzel RG, Eigenbrodt E, et al. Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal cancer. Br J Cancer. 2004; 91 (5): 980-984.
33. 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 (7279): 364-368.
34. 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 (5): 1894-1899.
35. Burd CG, Dreyfuss G. RNA binding specificity of hnRNP A1: significance of hnRNP A1 high-affinity binding sites in pre-mRNA splicing. EMBO J. 1994; 13 (5): 1197-1204.
36. Del Gatto-Konczak F, Olive M, Gesnel MC, Breathnach R. hnRNP A1 recruited to an exon in vivo can function as an exon splicing silencer. Mol Cell Biol. 1999; 19 (1): 251-260.
37. Chen M, Manley JL. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Biol. 2009; 10 (11): 741-754.
38. Grosso AR, Martins S, Carmo-Fonseca M. The emerging role of splicing factors in cancer. EMBO Rep. 2008; 9 (11): 1087-1093.
39. Zhou J, Allred DC, Avis I, Martinez A, Vos MD, Smith L, et al. Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein- A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic breast cancer. Breast cancer research and treatment. 2001; 66 (3): 217-224.
40. Hanamura A, Caceres JF, Mayeda A, Franza BR, Jr., Krainer AR. Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors. RNA. 1998; 4(4): 430-444.
41. Zerbe LK, Pino I, Pio R, Cosper PF, Dwyer-Nield LD, Meyer AM, et al. Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: implications for premRNA processing. Molecular carcinogenesis. 2004; 41 (4): 187-196.
42. Spellman R, Smith CW. Novel modes of splicing repression by PTB. Trends Biochem Sci. 2006; 31 (2): 73-76.
43. Singh R, Valcarcel J, Green MR. Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins. Science. 1995; 268 (5214): 1173-1176.
44. Sauliere J, Sureau A, Expert-Bezancon A, Marie J. The polypyrimidine tract binding protein (PTB) represses splicing of exon 6B from the beta-tropomyosin premRNA by directly interfering with the binding of the U2AF65 subunit. Mol Cell Biol. 2006; 26 (23): 8755-8769.
45. Valcarcel J, Singh R, Zamore PD, Green MR. The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer premRNA. Nature. 1993; 362 (6416): 171-175.
46. Shibayama M, Ohno S, Osaka T, Sakamoto R, Tokunaga A, Nakatake Y, et al. Polypyrimidine tract-binding protein is essential for early mouse development and embryonic stem cell proliferation. FEBS J. 2009; 276 (22): 6658-6668.
47. He X, Pool M, Darcy KM, Lim SB, Auersperg N, Coon JS, et al. Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro. Oncogene. 2007; 26 (34): 4961-498.
48. Takenaka M, Yamada K, Lu T, Kang R, Tanaka T, Noguchi T. Alternative splicing of the pyruvate kinase M gene in a minigene system. Eur J Biochem. 1996; 235 (1-2): 366-371.
49. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126 (4): 663-676.
50. Chen M, Zhang J, Manley JL. Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA. Cancer Res. 2010; 70 (22): 8977-8980.
51. Sun Q, Chen X, Ma J, Peng H, Wang F, 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 Sci U S A. 2011; 108 (10): 4129-4134.
52. Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 2010; 330 (6009): 1340-1344.
53. 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 (5): 732-744.
54. Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. The international journal of biochemistry & cell biology. 2011; 43 (7): 969-980.
55. 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. Science signaling. 2009; 2 (97): ra73.
56. 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 (5998): 1492-1499.
57. Postma PW, Lengeler JW, Jacobson GR. Phosphoenolpyruvate: carbohydrate phosphotransferase systems of bacteria. Microbiol Rev. 1993; 57 (3): 543-594.
58. Saier MH, Jr., Ye JJ, Klinke S, Nino E. Identification of an anaerobically induced phosphoenolpyruvatedependent fructose-specific phosphotransferase system and evidence for the Embden-Meyerhof glycolytic pathway in the heterofermentative bacterium Lactobacillus brevis. J Bacteriol. 1996; 178 (1): 314-316.
59. Fothergill-Gilmore LA, Watson HC. The phosphoglycerate mutases. Adv Enzymol Relat Areas Mol Biol. 1989; 62: 227-313.
60. Engel M, Mazurek S, Eigenbrodt E, Welter C. Phosphoglycerate mutase-derived polypeptide inhibits glycolytic flux and induces cell growth arrest in tumor cell lines. The Journal of biological chemistry. 2004; 279 (34): 35803-35812.