PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop

Oncotarget

Volumn 6, Issue 15, 2015, Pages 13006-13018

  Luan, Wenkang ^a   Wang, Yingyi ^a   Chen, Xincheng ^a   Shi, Yan ^a   Wang, Jiajia ^a   Zhang, Junxia ^a   Qian, Jin ^b   Li, Ri ^a   Tao, Tao ^a   Wei, Wenjin ^a   Hu, Qi ^a   Liu, Ning ^a   You, Yongping ^a  

^a THE FIRST AFFILIATED HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

^b Neurol Dept of Shaanxi Province   (China)

Author keywords

Aerobic glycolysis; c Myc; Glioma; Glucose metabolism; HnRNPA1; Let 7a microRNA; PKM2

Indexed keywords

GLUCOSE; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A1; MESSENGER RNA PRECURSOR; MICRORNA; MICRORNA LET7A; MYC PROTEIN; PYRUVATE KINASE; PYRUVATE KINASE ISOENZYME TYPE M2; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; CARRIER PROTEIN; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN GROUP A B; HNRNP A1; MEMBRANE PROTEIN; MIRNLET7 MICRORNA, HUMAN; MYC PROTEIN, HUMAN; THYROID HORMONE; THYROID HORMONE-BINDING PROTEINS;

ARTICLE; CANCER CELL; CELL GROWTH; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; FEEDBACK SYSTEM; GLIOMA CELL; GLUCOSE METABOLISM; GLYCOLYSIS; HUMAN; HUMAN CELL; INHIBITION KINETICS; PROTEIN BINDING; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; UPREGULATION; ANIMAL; FEMALE; GENETIC TRANSFECTION; GENETICS; GLIOMA; METABOLISM; MOUSE; NUDE MOUSE; PATHOLOGY; PHYSIOLOGY; TUMOR CELL LINE; XENOGRAFT;

ANIMALS; CARRIER PROTEINS; CELL GROWTH PROCESSES; CELL LINE, TUMOR; FEEDBACK, PHYSIOLOGICAL; FEMALE; GLIOMA; GLUCOSE; GLYCOLYSIS; HETEROGENEOUS-NUCLEAR RIBONUCLEOPROTEIN GROUP A-B; HETEROGRAFTS; HUMANS; MEMBRANE PROTEINS; MICE; MICE, NUDE; MICRORNAS; PROTO-ONCOGENE PROTEINS C-MYC; PYRUVATE KINASE; SIGNAL TRANSDUCTION; THYROID HORMONES; TRANSFECTION;

EID: 84931058595     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.3514     Document Type: Article

References (30)

1. Hanahan D and Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-674.
2. Vander Heiden MG, Cantley LC and Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324(5930):1029-1033.
3. Warburg O. On the origin of cancer cells. Science. 1956; 123(3191):309-314.
4. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S and Thompson CB. Beyond aerobic glycolysis:transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(49):19345-19350.
5. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008; 321(5897):1807-1812.
6. Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R, Hawkins C and Guha A. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. The Journal of experimental medicine. 2011; 208(2):313-326.
7. 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.
8. Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, Wang Y, Jing Y, Yang H, Chen R, Chang L, Zhang Y, Goto J, Onda H, Chen T, Wang MR, et al. Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108(10):4129-4134.
9. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL and Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008; 452(7184):230-233.
10. Peng XC, Gong FM, Zhao YW, Zhou LX, Xie YW, Liao HL, Lin HJ, Li ZY, Tang MH and Tong AP. Comparative proteomic approach identifies PKM2 and cofilin-1 as potential diagnostic, prognostic and therapeutic targets for pulmonary adenocarcinoma. PloS one. 2011; 6(11):e27309.
11. Kosugi M, Ahmad R, Alam M, Uchida Y and Kufe D. MUC1-C oncoprotein regulates glycolysis and pyruvate kinase M2 activity in cancer cells. PloS one. 2011; 6(11):e28234.
12. David CJ, Chen M, Assanah M, Canoll P and Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature. 2010; 463(7279):364-368.
13. Wang XR, Luo H, Li HL, Cao L, Wang XF, Yan W, Wang YY, Zhang JX, Jiang T, Kang CS, Liu N, You YP and Chinese Glioma Cooperative G. Overexpressed let-7a inhibits glioma cell malignancy by directly targeting K-ras, independently of PTEN. Neuro-oncology. 2013; 15(11):1491-1501.
14. Michlewski G and Caceres JF. Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis. Nature structural & molecular biology. 2010; 17(8):1011-1018.
15. Chaneton B and Gottlieb E. Rocking cell metabolism:revised functions of the key glycolytic regulator PKM2 in cancer. Trends in biochemical sciences. 2012; 37(8):309-316.
16. Harada K, Saheki S, Wada K and Tanaka T. Purification of four pyruvate kinase isozymes of rats by affinity elution chromatography. Biochimica et biophysica acta. 1978; 524(2):327-339.
17. Mazurek S, Boschek CB, Hugo F and Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Seminars in cancer biology. 2005; 15(4):300-308.
18. Zwerschke W, Mazurek S, Massimi P, Banks L, Eigenbrodt E and Jansen-Durr P. Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proceedings of the National Academy of Sciences of the United States of America. 1999; 96(4):1291-1296.
19. Mazurek S, Boschek CB and Eigenbrodt E. The role of phosphometabolites in cell proliferation, energy metabolism, and tumor therapy. Journal of bioenergetics and biomembranes. 1997; 29(4):315-330.
20. Mazurek S, Drexler HC, Troppmair J, Eigenbrodt E and Rapp UR. Regulation of pyruvate kinase type M2 by A-Raf:a possible glycolytic stop or go mechanism. Anticancer research. 2007; 27(6B):3963-3971.
21. Wu H, Li Z, Yang P, Zhang L, Fan Y and Li Z. PKM2 depletion induces the compensation of glutaminolysis through beta-catenin/c-Myc pathway in tumor cells. Cellular signalling. 2014; 26(11):2397-2405.
22. Hamabe A, Konno M, Tanuma N, Shima H, Tsunekuni K, Kawamoto K, Nishida N, Koseki J, Mimori K, Gotoh N, Yamamoto H, Doki Y, Mori M and Ishii H. Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial-mesenchymal transition. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111(43):15526-15531.
23. Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG and Krainer AR. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(5):1894-1899.
24. Chen M, Zhang J and Manley JL. Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA. Cancer research. 2010; 70(22):8977-8980.
25. Han J, Lee Y, Yeom KH, Kim YK, Jin H and Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes & development. 2004; 18(24):3016-3027.
26. Zeng Y and Cullen BR. Recognition and cleavage of primary microRNA transcripts. Methods in molecular biology. 2006; 342:49-56.
27. Kim VN, Han J and Siomi MC. Biogenesis of small RNAs in animals. Nature reviews Molecular cell biology. 2009; 10(2):126-139.
28. Ruggiero T, Trabucchi M, De Santa F, Zupo S, Harfe BD, McManus MT, Rosenfeld MG, Briata P and Gherzi R. LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2009; 23(9):2898-2908.
29. Trabucchi M, Briata P, Garcia-Mayoral M, Haase AD, Filipowicz W, Ramos A, Gherzi R and Rosenfeld MG. The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature. 2009; 459(7249):1010-1014.
30. Zhang C, Hao L, Wang L, Xiao Y, Ge H, Zhu Z, Luo Y, Zhang Y and Zhang Y. Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer. BMC cancer. 2010; 10:184.