The sweet trap in tumors: Aerobic glycolysis and potential targets for therapy

Oncotarget

Volumn 7, Issue 25, 2016, Pages 38908-38926

  Yu, Li ^a   Chen, Xun ^a   Wang, Liantang ^a   Chen, Shangwu ^a  

^a SUN YAT SEN UNIVERSITY   (China)

Author keywords

Aerobic glycolysis; Glucose metabolism; Targets for the tumor therapy; Warburg effect

Indexed keywords

6 PHOSPHOFRUCTO 2 KINASE; 6 PHOSPHOFRUCTOKINASE; ADENOSINE PHOSPHATE; GLUCOSE; GLUCOSE REGULATED PROTEIN 78; GLUCOSE TRANSPORTER; GLUCOSE TRANSPORTER 1; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; HEXOKINASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; K RAS PROTEIN; KRUPPEL LIKE FACTOR 4; LACTATE DEHYDROGENASE; MICRORNA; MONOCARBOXYLATE TRANSPORTER; MYC PROTEIN; OXYGEN; POLYPYRIMIDINE TRACT BINDING PROTEIN; PROTEIN KINASE; PYRUVATE KINASE; ANTINEOPLASTIC AGENT; ONCOPROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; TARGET OF RAPAMYCIN KINASE;

AEROBIC GLYCOLYSIS; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE MARROW CANCER; BREAST CANCER; CANCER CELL; CANCER THERAPY; CELL PROLIFERATION; CITRIC ACID CYCLE; ENERGY YIELD; GLIOBLASTOMA; GLIOMA CELL; GLUCOSE INTAKE; GLYCOLYSIS; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LIVER CANCER; LUNG CANCER; LYMPHOMA; MITOCHONDRIAL RESPIRATION; MULTIPLE CANCER; OSTEOSARCOMA; OXIDATIVE PHOSPHORYLATION; PANCREAS CANCER; PROSTATE CANCER; STOMACH CANCER; TUMOR CELL; AEROBIC METABOLISM; ANIMAL; CHEMISTRY; GENE EXPRESSION REGULATION; METABOLISM; MITOCHONDRION; NEOPLASM; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

AEROBIOSIS; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUCOSE; GLYCOLYSIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MITOCHONDRIA; NEOPLASMS; ONCOGENE PROTEIN V-AKT; OXYGEN; PHOSPHATIDYLINOSITOL 3-KINASES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84964631713     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.7676     Document Type: Article

References (189)

1. Hanahan D and Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-674.
2. Warburg O, Wind F and Negelein E. The Metabolism of Tumors in the Body. J Gen Physiol. 1927; 8(6):519-530.
3. Vander Heiden MG, Cantley LC and Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324(5930):1029-1033.
4. Warburg O. On the origin of cancer cells. Science. 1956; 123(3191):309-314.
5. Nolop KB, Rhodes CG, Brudin LH, Beaney RP, Krausz T, Jones T and Hughes JM. Glucose utilization in vivo by human pulmonary neoplasms. Cancer. 1987; 60(11):2682-2689.
6. Gottschalk S, Anderson N, Hainz C, Eckhardt SG and Serkova NJ. Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res. 2004; 10(19):6661-6668.
7. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B and Michelakis ED. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007; 11(1):37-51.
8. Bomanji JB, Costa DC and Ell PJ. Clinical role of positron emission tomography in oncology. Lancet Oncol. 2001; 2(3):157-164.
9. Rodrigues TB, Serrao EM, Kennedy BW, Hu DE, Kettunen MI and Brindle KM. Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose. Nat Med. 2014; 20(1):93-97.
10. Walker-Samuel S, Ramasawmy R, Torrealdea F, Rega M, Rajkumar V, Johnson SP, Richardson S, Goncalves M, Parkes HG, Arstad E, Thomas DL, Pedley RB, Lythgoe MF and Golay X. In vivo imaging of glucose uptake and metabolism in tumors. Nat Med. 2013; 19(8):1067-1072.
11. Hu Y, Lu W, Chen G, Wang P, Chen Z, Zhou Y, Ogasawara M, Trachootham D, Feng L, Pelicano H, Chiao PJ, Keating MJ, Garcia-Manero G and Huang P. K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis. Cell Res. 2012; 22(2):399-412.
12. Lu W, Hu Y, Chen G, Chen Z, Zhang H, Wang F, Feng L, Pelicano H, Wang H, Keating MJ, Liu J, McKeehan W, Luo Y and Huang P. Novel role of NOX in supporting aerobic glycolysis in cancer cells with mitochondrial dysfunction and as a potential target for cancer therapy. PLoS Biol. 2012; 10(5):e1001326.
13. Ganapathy-Kanniappan S and Geschwind JF. Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer. 2013; 12:152.
14. Guppy M, Leedman P, Zu X and Russell V. Contribution by different fuels and metabolic pathways to the total ATP turnover of proliferating MCF-7 breast cancer cells. Biochem J. 2002; 364(Pt 1):309-315.
15. Martin M, Beauvoit B, Voisin PJ, Canioni P, Guerin B and Rigoulet M. Energetic and morphological plasticity of C6 glioma cells grown on 3-D support; effect of transient glutamine deprivation. J Bioenerg Biomembr. 1998; 30(6):565-578.
16. Pasdois P, Deveaud C, Voisin P, Bouchaud V, Rigoulet M and Beauvoit B. Contribution of the phosphorylable complex I in the growth phase-dependent respiration of C6 glioma cells in vitro. J Bioenerg Biomembr. 2003; 35(5):439-450.
17. Moreno-Sanchez R, Rodriguez-Enriquez S, Marin-Hernandez A and Saavedra E. Energy metabolism in tumor cells. FEBS J. 2007; 274(6):1393-1418.
18. Cavalli LR, Varella-Garcia M and Liang BC. Diminished tumorigenic phenotype after depletion of mitochondrial DNA. Cell Growth Differ. 1997; 8(11):1189-1198.
19. de Souza AC, Justo GZ, de Araujo DR and Cavagis AD. Defining the molecular basis of tumor metabolism: a continuing challenge since Warburg's discovery. Cell Physiol Biochem. 2011; 28(5):771-792.
20. Locasale JW and Cantley LC. Altered metabolism in cancer. BMC Biol. 2010; 8:88.
21. Gatenby RA and Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004; 4(11):891-899.
22. Lunt SY and Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011; 27:441-464.
23. Hamanaka RB and Chandel NS. Targeting glucose metabolism for cancer therapy. J Exp Med. 2012; 209(2):211-215.
24. Deberardinis RJ, Sayed N, Ditsworth D and Thompson CB. Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev. 2008; 18(1):54-61.
25. Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, Christofk HR, Wagner G, Rabinowitz JD, Asara JM and Cantley LC. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science. 2010; 329(5998):1492-1499.
26. Folmes CD, Nelson TJ, Martinez-Fernandez A, Arrell DK, Lindor JZ, Dzeja PP, Ikeda Y, Perez-Terzic C and Terzic A. Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 2011; 14(2):264-271.
27. Panopoulos AD, Yanes O, Ruiz S, Kida YS, Diep D, Tautenhahn R, Herrerias A, Batchelder EM, Plongthongkum N, Lutz M, Berggren WT, Zhang K, Evans RM, Siuzdak G and Izpisua Belmonte JC. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 2012; 22(1):168-177.
28. Zhu S, Li W, Zhou H, Wei W, Ambasudhan R, Lin T, Kim J, Zhang K and Ding S. Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell. 2010; 7(6):651-655.
29. Fu X, Zhu MJ, Dodson MV and Du M. AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration. J Biol Chem. 2015; 290(44):26445-26456.
30. Moussaieff A, Rouleau M, Kitsberg D, Cohen M, Levy G, Barasch D, Nemirovski A, Shen-Orr S, Laevsky I, Amit M, Bomze D, Elena-Herrmann B, Scherf T, Nissim-Rafinia M, Kempa S, Itskovitz-Eldor J, et al. Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab. 2015; 21(3):392-402.
31. Du W, Amarachintha S, Wilson AF and Pang Q. SCO2 mediates oxidative stress-induced glycolysis to OXPHOS switch in hematopoietic stem cells. Stem Cells. 2015 Dec 16 doi: 10.1002/stem.2260. [Epub ahead of print]
32. Wang T, Marquardt C and Foker J. Aerobic glycolysis during lymphocyte proliferation. Nature. 1976; 261(5562):702-705.
33. Maciver NJ, Jacobs SR, Wieman HL, Wofford JA, Coloff JL and Rathmell JC. Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. J Leukoc Biol. 2008; 84(4):949-957.
34. Stark H, Fichtner M, Konig R, Lorkowski S and Schuster S. Causes of upregulation of glycolysis in lymphocytes upon stimulation. A comparison with other cell types. Biochimie. 2015; 118:185-194.
35. Chang CH, Curtis JD, Maggi LB, Jr., Faubert B, Villarino AV, O'Sullivan D, Huang SC, van der Windt GJ, Blagih J, Qiu J, Weber JD, Pearce EJ, Jones RG and Pearce EL. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell. 2013; 153(6):1239-1251.
36. Pearce EL, Poffenberger MC, Chang CH and Jones RG. Fueling immunity: insights into metabolism and lymphocyte function. Science. 2013; 342(6155):1242454.
37. Ou J, Miao H, Ma Y, Guo F, Deng J, Wei X, Zhou J, Xie G, Shi H, Xue B, Liang H and Yu L. Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition. Cell Rep. 2014; 9(5):1798-1811.
38. Ha TK and Chi SG. CAV1/caveolin 1 enhances aerobic glycolysis in colon cancer cells via activation of SLC2A3/GLUT3 transcription. Autophagy. 2012; 8(11):1684-1685.
39. Ha TK, Her NG, Lee MG, Ryu BK, Lee JH, Han J, Jeong SI, Kang MJ, Kim NH, Kim HJ and Chi SG. Caveolin-1 increases aerobic glycolysis in colorectal cancers by stimulating HMGA1-mediated GLUT3 transcription. Cancer Res. 2012; 72(16):4097-4109.
40. Tahir SA, Yang G, Goltsov A, Song KD, Ren C, Wang J, Chang W and Thompson TC. Caveolin-1-LRP6 signaling module stimulates aerobic glycolysis in prostate cancer. Cancer Res. 2013; 73(6):1900-1911.
41. Ke X, Fei F, Chen Y, Xu L, Zhang Z, Huang Q, Zhang H, Yang H, Chen Z and Xing J. Hypoxia upregulates CD147 through a combined effect of HIF-1alpha and Sp1 to promote glycolysis and tumor progression in epithelial solid tumors. Carcinogenesis. 2012; 33(8):1598-1607.
42. Huang Q, Li J, Xing J, Li W, Li H, Ke X, Zhang J, Ren T, Shang Y, Yang H, Jiang J and Chen Z. CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting the p53-dependent signaling pathway. J Hepatol. 2014; 61(4):859-866.
43. Huang P, Chang S, Jiang X, Su J, Dong C, Liu X, Yuan Z, Zhang Z and Liao H. RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis. Int J Clin Exp Pathol. 2015; 8(1):309-318.
44. Dey P, Rachagani S, Chakraborty S, Singh PK, Zhao X, Gurumurthy CB, Anderson JM, Lele S, Hollingsworth MA, Band V and Batra SK. Overexpression of ecdysoneless in pancreatic cancer and its role in oncogenesis by regulating glycolysis. Clin Cancer Res. 2012; 18(22):6188-6198.
45. Zhang J, Gao Q, Zhou Y, Dier U, Hempel N and Hochwald SN. Focal adhesion kinase-promoted tumor glucose metabolism is associated with a shift of mitochondrial respiration to glycolysis. Oncogene. 2015 Jun 29. doi: 10.1038/onc.2015.256. [Epub ahead of print]
46. Zhang XY, Li M, Sun K, Chen XJ, Meng J, Wu L, Zhang P, Tong X and Jiang WW. Decreased expression of GRIM-19 by DNA hypermethylation promotes aerobic glycolysis and cell proliferation in head and neck squamous cell carcinoma. Oncotarget. 2015; 6(1):101-115. doi: 10.18632/oncotarget.2684.
47. Li Z, Wang Y, Newton IP, Zhang L and Ji P. GRP78 is implicated in the modulation of tumor aerobic glycolysis by promoting autophagic degradation of IKKbeta. Cell Signal. 2015; 27(6):1237-45.
48. Dang CV, Kim JW, Gao P and Yustein J. The interplay between MYC and HIF in cancer. Nat Rev Cancer. 2008; 8(1):51-56.
49. Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 2008; 8(9):705-713.
50. Rempel A, Mathupala SP, Griffin CA, Hawkins AL and Pedersen PL. Glucose catabolism in cancer cells: amplification of the gene encoding type II hexokinase. Cancer Res. 1996; 56(11):2468-2471.
51. Kim JW, Tchernyshyov I, Semenza GL and Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006; 3(3):177-185.
52. Papandreou I, Cairns RA, Fontana L, Lim AL and Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006; 3(3):187-197.
53. Huang L, Yu Z, Zhang T, Zhao X and Huang G. HSP40 interacts with pyruvate kinase M2 and regulates glycolysis and cell proliferation in tumor cells. PLoS One. 2014; 9(3):e92949.
54. Shi M, Cui J, Du J, Wei D, Jia Z, Zhang J, Zhu Z, Gao Y and Xie K. A novel KLF4/LDHA signaling pathway regulates aerobic glycolysis in and progression of pancreatic cancer. Clin Cancer Res. 2014; 20(16):4370-4380.
55. Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, Schmidt K, Willson JK, Markowitz S, Zhou S, Diaz LA, Jr., Velculescu VE, Lengauer C, Kinzler KW, Vogelstein B and Papadopoulos N. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 2009; 325(5947):1555-1559.
56. Ma T, Patel H, Babapoor-Farrokhran S, Franklin R, Semenza GL, Sodhi A and Montaner S. KSHV induces aerobic glycolysis and angiogenesis through HIF-1-dependent upregulation of pyruvate kinase 2 in Kaposi's sarcoma. Angiogenesis. 2015; 18(4):477-88.
57. Lo AK, Dawson CW, Young LS, Ko CW, Hau PM and Lo KW. Activation of the FGFR1 signalling pathway by the Epstein-Barr virus-encoded LMP1 promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells. J Pathol. 2015 Jun 15. doi: 10.1002/path.4575. [Epub ahead of print]
58. Fang R, Xiao T, Fang Z, Sun Y, Li F, Gao Y, Feng Y, Li L, Wang Y, Liu X, Chen H, Liu XY and Ji H. MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene. J Biol Chem. 2012; 287(27):23227-23235.
59. Zhao S, Liu H, Liu Y, Wu J, Wang C, Hou X, Chen X, Yang G, Zhao L, Che H, Bi Y, Wang H, Peng F and Ai J. miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells. Cancer Lett. 2013; 333(2):253-260.
60. Guo W, Qiu Z, Wang Z, Wang Q, Tan N, Chen T, Chen Z, Huang S, Gu J, Li J, Yao M, Zhao Y and He X. MiR-199a-5p is negatively associated with malignancies and regulates glycolysis and lactate production by targeting hexokinase 2 in liver cancer. Hepatology. 2015; 62(4):1132-44.
61. Wang J, Wang H, Liu A, Fang C, Hao J and Wang Z. Lactate dehydrogenase A negatively regulated by miRNAs promotes aerobic glycolysis and is increased in colorectal cancer. Oncotarget. 2015; 6(23):19456-19468. doi: 10.18632/oncotarget.3318.
62. Du JY, Wang LF, Wang Q and Yu LD. miR-26b inhibits proliferation, migration, invasion and apoptosis induction via the downregulation of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase-3 driven glycolysis in osteosarcoma cells. Oncol Rep. 2015; 33(4):1890-1898.
63. Tang H, Lee M, Sharpe O, Salamone L, Noonan EJ, Hoang CD, Levine S, Robinson WH and Shrager JB. Oxidative stress-responsive microRNA-320 regulates glycolysis in diverse biological systems. FASEB J. 2012; 26(11):4710-4721.
64. Fan JY, Yang Y, Xie JY, Lu YL, Shi K and Huang YQ. MicroRNA-144 mediates metabolic shift in ovarian cancer cells by directly targeting Glut1. Tumour Biol. 2015 Dec. 11 [Epub ahead of print]
65. Chen B, Tang H, Liu X, Liu P, Yang L, Xie X, Ye F, Song C and Wei W. miR-22 as a prognostic factor targets glucose transporter protein type 1 in breast cancer. Cancer Lett. 2015; 356(2 Pt B):410-417.
66. Yamasaki T, Seki N, Yoshino H, Itesako T, Yamada Y, Tatarano S, Hidaka H, Yonezawa T, Nakagawa M and Enokida H. Tumor-suppressive microRNA-1291 directly regulates glucose transporter 1 in renal cell carcinoma. Cancer Sci. 2013; 104(11):1411-1419.
67. Fei X, Qi M, Wu B, Song Y, Wang Y and Li T. MicroRNA-195-5p suppresses glucose uptake and proliferation of human bladder cancer T24 cells by regulating GLUT3 expression. FEBS Lett. 2012; 586(4):392-397.
68. Peschiaroli A, Giacobbe A, Formosa A, Markert EK, Bongiorno-Borbone L, Levine AJ, Candi E, D'Alessandro A, Zolla L, Finazzi Agro A and Melino G. miR-143 regulates hexokinase 2 expression in cancer cells. Oncogene. 2012; 32(6):797-802.
69. Gregersen LH, Jacobsen A, Frankel LB, Wen J, Krogh A and Lund AH. MicroRNA-143 down-regulates Hexokinase 2 in colon cancer cells. BMC Cancer. 2012; 12:232.
70. Kawauchi K, Araki K, Tobiume K and Tanaka N. p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation. Nat Cell Biol. 2008; 10(5):611-618.
71. Kondoh H, Lleonart ME, Gil J, Wang J, Degan P, Peters G, Martinez D, Carnero A and Beach D. Glycolytic enzymes can modulate cellular life span. Cancer Res. 2005; 65(1):177-185.
72. Madan E, Gogna R, Bhatt M, Pati U, Kuppusamy P and Mahdi AA. Regulation of glucose metabolism by p53: emerging new roles for the tumor suppressor. Oncotarget. 2011; 2(12):948-957. doi: 10.18632/oncotarget.389.
73. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E and Vousden KH. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006; 126(1):107-120.
74. Jiang P, Du W, Wang X, Mancuso A, Gao X, Wu M and Yang X. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol. 2011; 13(3):310-316.
75. Feng Z, Hu W, de Stanchina E, Teresky AK, Jin S, Lowe S and Levine AJ. The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res. 2007; 67(7):3043-3053.
76. Budanov AV and Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell. 2008; 134(3):451-460.
77. Zhang C, Liu J, Wu R, Liang Y, Lin M, Chan CS, Hu W and Feng Z. Tumor suppressor p53 negatively regulates glycolysis stimulated by hypoxia through its target RRAD. Oncotarget. 2014; 5(14):5535-5546. doi: 10.18632/oncotarget.2137.
78. Amoroso F, Falzoni S, Adinolfi E, Ferrari D and Di Virgilio F. The P2X7 receptor is a key modulator of aerobic glycolysis. Cell Death Dis. 2012; 3:e370.
79. Csibi A and Blenis J. Appetite for destruction: the inhibition of glycolysis as a therapy for tuberous sclerosis complexrelated tumors. BMC Biol. 2011; 9:69.
80. Jiang X, Kenerson H, Aicher L, Miyaoka R, Eary J, Bissler J and Yeung RS. The tuberous sclerosis complex regulates trafficking of glucose transporters and glucose uptake. Am J Pathol. 2008; 172(6):1748-1756.
81. Duvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, MacKeigan JP, Finan PM, Clish CB, Murphy LO and Manning BD. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell. 2010; 39(2):171-183.
82. 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. Proc Natl Acad Sci U S A. 2011; 108(10):4129-4134.
83. Zha X, Hu Z, Ji S, Jin F, Jiang K, Li C, Zhao P, Tu Z, Chen X, Di L, Zhou H and Zhang H. NFkappaB up-regulation of glucose transporter 3 is essential for hyperactive mammalian target of rapamycin-induced aerobic glycolysis and tumor growth. Cancer Lett. 2015; 359(1):97-106.
84. Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Feng Z, Huang HY, Tsai KK, Flores LG, Shao Y, Hazle JD, Yu D, Wei W, Sarbassov D, Hung MC, Nakayama KI, et al. The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis. Cell. 2012; 149(5):1098-1111.
85. Hagenbuchner J, Kuznetsov AV, Obexer P and Ausserlechner MJ. BIRC5/Survivin enhances aerobic glycolysis and drug resistance by altered regulation of the mitochondrial fusion/fission machinery. Oncogene. 2013; 32(40):4748-4757.
86. Yoshida S, Tsutsumi S, Muhlebach G, Sourbier C, Lee MJ, Lee S, Vartholomaiou E, Tatokoro M, Beebe K, Miyajima N, Mohney RP, Chen Y, Hasumi H, Xu W, Fukushima H, Nakamura K, et al. Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis. Proc Natl Acad Sci U S A. 2013; 110(17):E1604-1612.
87. Pate KT, Stringari C, Sprowl-Tanio S, Wang K, TeSlaa T, Hoverter NP, McQuade MM, Garner C, Digman MA, Teitell MA, Edwards RA, Gratton E and Waterman ML. Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer. EMBO J. 2014; 33(13):1454-1473.
88. Liu XS, Haines JE, Mehanna EK, Genet MD, Ben-Sahra I, Asara JM, Manning BD and Yuan ZM. ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis. Genes Dev. 2014; 28(17):1917-1928.
89. Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM and Thompson CB. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 2004; 64(11):3892-3899.
90. Zhuo B, Li Y, Li Z, Qin H, Sun Q, Zhang F, Shen Y, Shi Y and Wang R. PI3K/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma. Biochem Biophys Res Commun. 2015; 464(2):401-406.
91. Li W, Peng C, Lee MH, Lim D, Zhu F, Fu Y, Yang G, Sheng Y, Xiao L, Dong X, Ma W, Bode AM, Cao Y and Dong Z. TRAF4 is a critical molecule for Akt activation in lung cancer. Cancer Res. 2013; 73(23):6938-6950.
92. Deprez J, Vertommen D, Alessi DR, Hue L and Rider MH. Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. J Biol Chem. 1997; 272(28):17269-17275.
93. Barthel A, Okino ST, Liao J, Nakatani K, Li J, Whitlock JP, Jr. and Roth RA. Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J Biol Chem. 1999; 274(29):20281-20286.
94. Robey RB and Hay N. Is Akt the "Warburg kinase"?-Aktenergy metabolism interactions and oncogenesis. Semin Cancer Biol. 2009; 19(1):25-31.
95. Shimura T, Noma N, Sano Y, Ochiai Y, Oikawa T, Fukumoto M and Kunugita N. AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells. Radiother Oncol. 2014; 112(2):302-307.
96. Inoki K, Li Y, Zhu T, Wu J and Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002; 4(9):648-657.
97. Inoki K, Corradetti MN and Guan KL. Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet. 2005; 37(1):19-24.
98. Ran C, Liu H, Hitoshi Y and Israel MA. Proliferationindependent control of tumor glycolysis by PDGFRmediated AKT activation. Cancer Res. 2013; 73(6):1831-1843.
99. Makinoshima H, Takita M, Saruwatari K, Umemura S, Obata Y, Ishii G, Matsumoto S, Sugiyama E, Ochiai A, Abe R, Goto K, Esumi H and Tsuchihara K. Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma. J Biol Chem. 2015; 290(28):17495-17504.
100. Landis J and Shaw LM. Insulin receptor substrate 2-mediated phosphatidylinositol 3-kinase signaling selectively inhibits glycogen synthase kinase 3beta to regulate aerobic glycolysis. J Biol Chem. 2014; 289(26):18603-18613.
101. Wang L, Xiong H, Wu F, Zhang Y, Wang J, Zhao L, Guo X, Chang LJ, You MJ, Koochekpour S, Saleem M, Huang H, Lu J and Deng Y. Hexokinase 2-mediated Warburg effect is required for PTEN-and p53-deficiency-driven prostate cancer growth. Cell Rep. 2014; 8(5):1461-1474.
102. Garcia-Cao I, Song MS, Hobbs RM, Laurent G, Giorgi C, de Boer VC, Anastasiou D, Ito K, Sasaki AT, Rameh L, Carracedo A, Vander Heiden MG, Cantley LC, Pinton P, Haigis MC and Pandolfi PP. Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell. 2012; 149(1):49-62.
103. Liu G, Bi Y, Shen B, Yang H, Zhang Y, Wang X, Liu H, Lu Y, Liao J, Chen X and Chu Y. SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors by orchestrating HIF-1alpha-dependent glycolysis. Cancer Res. 2014; 74(3):727-737.
104. Shukla SK, Gunda V, Abrego J, Haridas D, Mishra A, Souchek J, Chaika NV, Yu F, Sasson AR, Lazenby AJ, Batra SK and Singh PK. MUC16-mediated activation of mTOR and c-Myc reprograms pancreatic cancer metabolism. Oncotarget. 2015; 6(22):19118-19131. doi: 10.18632/oncotarget.4078.
105. Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik JH, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 2012; 149(3):656-670.
106. Liang Y, Liu J and Feng Z. The regulation of cellular metabolism by tumor suppressor p53. Cell Biosci. 2013; 3(1):9.
107. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F and Hwang PM. p53 regulates mitochondrial respiration. Science. 2006; 312(5780):1650-1653.
108. Schwartzenberg-Bar-Yoseph F, Armoni M and Karnieli E. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res. 2004; 64(7):2627-2633.
109. Zhang C, Liu J, Liang Y, Wu R, Zhao Y, Hong X, Lin M, Yu H, Liu L, Levine AJ, Hu W and Feng Z. Tumourassociated mutant p53 drives the Warburg effect. Nat Commun. 2013; 4:2935.
110. Oakhill JS, Steel R, Chen ZP, Scott JW, Ling N, Tam S and Kemp BE. AMPK is a direct adenylate charge-regulated protein kinase. Science. 2011; 332(6036):1433-1435.
111. Hardie DG, Ross FA and Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012; 13(4):251-262.
112. Hardie DG. Molecular Pathways: Is AMPK a Friend or a Foe in Cancer? Clin Cancer Res. 2015; 21(17):3836-3840.
113. Inoki K, Zhu T and Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell. 2003; 115(5):577-590.
114. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE and Shaw RJ. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008; 30(2):214-226.
115. Green AS, Chapuis N, Maciel TT, Willems L, Lambert M, Arnoult C, Boyer O, Bardet V, Park S, Foretz M, Viollet B, Ifrah N, Dreyfus F, Hermine O, Moura IC, Lacombe C, et al. The LKB1/AMPK signaling pathway has tumor suppressor activity in acute myeloid leukemia through the repression of mTOR-dependent oncogenic mRNA translation. Blood. 2010; 116(20):4262-4273.
116. Hoppe S, Bierhoff H, Cado I, Weber A, Tiebe M, Grummt I and Voit R. AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply. Proc Natl Acad Sci U S A. 2009; 106(42):17781-17786.
117. Dandapani M and Hardie DG. AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells? Biochem Soc Trans. 2013; 41(2):687-693.
118. Grahame Hardie D. AMP-activated protein kinase: a key regulator of energy balance with many roles in human disease. J Intern Med. 2014; 276(6):543-559.
119. Sui X, Xu Y, Yang J, Fang Y, Lou H, Han W, Zhang M, Chen W, Wang K, Li D, Jin W, Lou F, Zheng Y, Hu H, Gong L, Zhou X, et al. Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation. PLoS One. 2014; 9(5):e97781.
120. Shafaee A, Dastyar DZ, Islamian JP and Hatamian M. Inhibition of tumor energy pathways for targeted esophagus cancer therapy. Metabolism. 2015; 64(10):1193-1198.
121. Valera A, Pujol A, Gregori X, Riu E, Visa J and Bosch F. Evidence from transgenic mice that myc regulates hepatic glycolysis. FASEB J. 1995; 9(11):1067-1078.
122. Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA and Dang CV. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem. 2000; 275(29):21797-21800.
123. Gan L, Xiu R, Ren P, Yue M, Su H, Guo G, Xiao D, Yu J, Jiang H, Liu H, Hu G and Qing G. Metabolic targeting of oncogene MYC by selective activation of the protoncoupled monocarboxylate family of transporters. Oncogene. 2015 Oct 5. doi: 10.1038/onc.2015.360. [Epub ahead of print]
124. 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.
125. Luan W, Wang Y, Chen X, Shi Y, Wang J, Zhang J, Qian J, Li R, Tao T, Wei W, Hu Q, Liu N and You Y. PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop. Oncotarget. 2015; 6(15):13006-13018. doi: 10.18632/oncotarget.3514.
126. Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R and Dang CV. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci U S A. 1997; 94(13):6658-6663.
127. He TL, Zhang YJ, Jiang H, Li XH, Zhu H and Zheng KL. The c-Myc-LDHA axis positively regulates aerobic glycolysis and promotes tumor progression in pancreatic cancer. Med Oncol. 2015; 32(7):187.
128. Wang X, Duan W, Li X, Liu J, Li D, Ye L, Qian L, Yang A, Xu Q, Liu H, Fu Q, Wu E, Ma Q and Shen X. PTTG regulates the metabolic switch of ovarian cancer cells via the c-myc pathway. Oncotarget. 2015; 6(38):40959-40969. doi: 10.18632/oncotarget.5726.
129. Xu X, Li J, Sun X, Guo Y, Chu D, Wei L, Li X, Yang G, Liu X, Yao L, Zhang J and Shen L. Tumor suppressor NDRG2 inhibits glycolysis and glutaminolysis in colorectal cancer cells by repressing c-Myc expression. Oncotarget. 2015; 6(28):26161-26176. doi: 10.18632/oncotarget.4544.
130. Chen B, Li H, Zeng X, Yang P, Liu X, Zhao X and Liang S. Roles of microRNA on cancer cell metabolism. J Transl Med. 2012; 10:228.
131. Jiang S, Zhang LF, Zhang HW, Hu S, Lu MH, Liang S, Li B, Li Y, Li D, Wang ED and Liu MF. A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. EMBO J. 2012; 31(8):1985-1998.
132. Teng Y, Zhang Y, Qu K, Yang X, Fu J, Chen W and Li X. MicroRNA-29B (mir-29b) regulates the Warburg effect in ovarian cancer by targeting AKT2 and AKT3. Oncotarget. 2015; 6(38):40799-40814. doi: 10.18632/oncotarget.5695.
133. Ge X, Lyu P, Cao Z, Li J, Guo G, Xia W and Gu Y. Overexpression of miR-206 suppresses glycolysis, proliferation and migration in breast cancer cells via PFKFB3 targeting. Biochem Biophys Res Commun. 2015; 463(4):1115-1121.
134. Yang X, Cheng Y, Li P, Tao J, Deng X, Zhang X, Gu M, Lu Q and Yin C. A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis. Tumour Biol. 2015; 36(1):383-391.
135. Mondal S, Roy D, Camacho-Pereira J, Khurana A, Chini E, Yang L, Baddour J, Stilles K, Padmabandu S, Leung S, Kalloger S, Gilks B, Lowe V, Dierks T, Hammond E, Dredge K, et al. HSulf-1 deficiency dictates a metabolic reprograming of glycolysis and TCA cycle in ovarian cancer. Oncotarget. 2015; 6(32):33705-19. doi: 10.18632/oncotarget.5605.
136. Hagenbuchner J, Kiechl-Kohlendorfer U, Obexer P and Ausserlechner MJ. BIRC5/Survivin as a target for glycolysis inhibition in high-stage neuroblastoma. Oncogene. 2015 Jul 6. doi: 10.1038/onc.2015.264. [Epub ahead of print]
137. Shiraishi T, Verdone JE, Huang J, Kahlert UD, Hernandez JR, Torga G, Zarif JC, Epstein T, Gatenby R, McCartney A, Elisseeff JH, Mooney SM, An SS and Pienta KJ. Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells. Oncotarget. 2015; 6(1):130-143. doi: 10.18632/oncotarget.2766.
138. Guillaumond F, Leca J, Olivares O, Lavaut MN, Vidal N, Berthezene P, Dusetti NJ, Loncle C, Calvo E, Turrini O, Iovanna JL, Tomasini R and Vasseur S. Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proc Natl Acad Sci U S A. 2013; 110(10):3919-3924.
139. 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.
140. Fantin VR, St-Pierre J and Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006; 9(6):425-434.
141. Flaveny CA, Griffett K, El-Gendy Bel D, Kazantzis M, Sengupta M, Amelio AL, Chatterjee A, Walker J, Solt LA, Kamenecka TM and Burris TP. Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis. Cancer Cell. 2015; 28(1):42-56.
142. Rajeshkumar NV, Dutta P, Yabuuchi S, de Wilde RF, Martinez GV, Le A, Kamphorst JJ, Rabinowitz JD, Jain SK, Hidalgo M, Dang CV, Gillies RJ and Maitra A. Therapeutic Targeting of the Warburg Effect in Pancreatic Cancer Relies on an Absence of p53 Function. Cancer Res. 2015; 75(16):3355-3364.
143. Wood TE, Dalili S, Simpson CD, Hurren R, Mao X, Saiz FS, Gronda M, Eberhard Y, Minden MD, Bilan PJ, Klip A, Batey RA and Schimmer AD. A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death. Mol Cancer Ther. 2008; 7(11):3546-3555.
144. Wu CH, Ho YS, Tsai CY, Wang YJ, Tseng H, Wei PL, Lee CH, Liu RS and Lin SY. In vitro and in vivo study of phloretin-induced apoptosis in human liver cancer cells involving inhibition of type II glucose transporter. Int J Cancer. 2009; 124(9):2210-2219.
145. Liu Y, Cao Y, Zhang W, Bergmeier S, Qian Y, Akbar H, Colvin R, Ding J, Tong L, Wu S, Hines J and Chen X. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol Cancer Ther. 2012; 11(8):1672-1682.
146. Dwarakanath B and Jain V. Targeting glucose metabolism with 2-deoxy-D-glucose for improving cancer therapy. Future Oncol. 2009; 5(5):581-585.
147. Maschek G, Savaraj N, Priebe W, Braunschweiger P, Hamilton K, Tidmarsh GF, De Young LR and Lampidis TJ. 2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo. Cancer Res. 2004; 64(1):31-34.
148. Xian SL, Cao W, Zhang XD and Lu YF. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis. Oncol Lett. 2015; 9(2):739-744.
149. Jae HJ, Chung JW, Park HS, Lee MJ, Lee KC, Kim HC, Yoon JH, Chung H and Park JH. The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model. Korean J Radiol. 2009; 10(6):596-603.
150. Talekar M, Boreddy SR, Singh A and Amiji M. Tumor aerobic glycolysis: new insights into therapeutic strategies with targeted delivery. Expert Opin Biol Ther. 2014; 14(8):1145-1159.
151. Zhou Y, Lu N, Qiao C, Ni T, Li Z, Yu B, Guo Q and Wei L. FV-429 induces apoptosis and inhibits glycolysis by inhibiting Akt-mediated phosphorylation of hexokinase II in MDA-MB-231 cells. Mol Carcinog. 2015 Aug 10. doi: 10.1002/mc.22374. [Epub ahead of print]
152. Furtado CM, Marcondes MC, Sola-Penna M, de Souza ML and Zancan P. Clotrimazole preferentially inhibits human breast cancer cell proliferation, viability and glycolysis. PLoS One. 2012; 7(2):e30462.
153. Clem B, Telang S, Clem A, Yalcin A, Meier J, Simmons A, Rasku MA, Arumugam S, Dean WL, Eaton J, Lane A, Trent JO and Chesney J. Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Mol Cancer Ther. 2008; 7(1):110-120.
154. Vuyyuri SB, Rinkinen J, Worden E, Shim H, Lee S and Davis KR. Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells. PLoS One. 2013; 8(6):e67081.
155. Ganapathy-Kanniappan S, Kunjithapatham R and Geschwind JF. Glyceraldehyde-3-phosphate dehydrogenase: a promising target for molecular therapy in hepatocellular carcinoma. Oncotarget. 2012; 3(9):940-953. doi: 10.18632/oncotarget.623.
156. Ganapathy-Kanniappan S, Kunjithapatham R and Geschwind JF. Anticancer efficacy of the metabolic blocker 3-bromopyruvate: specific molecular targeting. Anticancer Res. 2013; 33(1):13-20.
157. Ganapathy-Kanniappan S, Vali M, Kunjithapatham R, Buijs M, Syed LH, Rao PP, Ota S, Kwak BK, Loffroy R and Geschwind JF. 3-bromopyruvate: a new targeted antiglycolytic agent and a promise for cancer therapy. Curr Pharm Biotechnol. 2010; 11(5):510-517.
158. Vander Heiden MG, Christofk HR, Schuman E, Subtelny AO, Sharfi H, Harlow EE, Xian J and Cantley LC. Identification of small molecule inhibitors of pyruvate kinase M2. Biochem Pharmacol. 2010; 79(8):1118-1124.
159. Goldberg MS and Sharp PA. Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression. J Exp Med. 2012; 209(2):217-224.
160. Chen J, Xie J, Jiang Z, Wang B, Wang Y and Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene. 2011; 30(42):4297-4306.
161. Shi HS, Li D, Zhang J, Wang YS, Yang L, Zhang HL, Wang XH, Mu B, Wang W, Ma Y, Guo FC and Wei YQ. Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice. Cancer Sci. 2010; 101(6):1447-1453.
162. Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL and Dang CV. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci U S A. 2010; 107(5):2037-2042.
163. Zhou M, Zhao Y, Ding Y, Liu H, Liu Z, Fodstad O, Riker AI, Kamarajugadda S, Lu J, Owen LB, Ledoux SP and Tan M. Warburg effect in chemosensitivity: targeting lactate dehydrogenase-A re-sensitizes taxol-resistant cancer cells to taxol. Mol Cancer. 2010; 9:33.
164. Granchi C, Roy S, Giacomelli C, Macchia M, Tuccinardi T, Martinelli A, Lanza M, Betti L, Giannaccini G, Lucacchini A, Funel N, Leon LG, Giovannetti E, Peters GJ, Palchaudhuri R, Calvaresi EC, et al. Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells. J Med Chem. 2011; 54(6):1599-1612.
165. Colen CB, Shen Y, Ghoddoussi F, Yu P, Francis TB, Koch BJ, Monterey MD, Galloway MP, Sloan AE and Mathupala SP. Metabolic targeting of lactate efflux by malignant glioma inhibits invasiveness and induces necrosis: an in vivo study. Neoplasia. 2011; 13(7):620-632.
166. Dunbar EM, Coats BS, Shroads AL, Langaee T, Lew A, Forder JR, Shuster JJ, Wagner DA and Stacpoole PW. Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors. Invest New Drugs. 2014; 32(3):452-464.
167. Lin G, Hill DK, Andrejeva G, Boult JK, Troy H, Fong AC, Orton MR, Panek R, Parkes HG, Jafar M, Koh DM, Robinson SP, Judson IR, Griffiths JR, Leach MO, Eykyn TR, et al. Dichloroacetate induces autophagy in colorectal cancer cells and tumours. Br J Cancer. 2014; 111(2):375-385.
168. Chan DA, Sutphin PD, Nguyen P, Turcotte S, Lai EW, Banh A, Reynolds GE, Chi JT, Wu J, Solow-Cordero DE, Bonnet M, Flanagan JU, Bouley DM, Graves EE, Denny WA, Hay MP, et al. Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality. Sci Transl Med. 2011; 3(94):94ra70.
169. Jiang X, Xin H, Ren Q, Gu J, Zhu L, Du F, Feng C, Xie Y, Sha X and Fang X. Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment. Biomaterials. 2014; 35(1):518-529.
170. Wilson JE. Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol. 2003; 206(Pt 12):2049-2057.
171. 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. J Exp Med. 2011; 208(2):313-326.
172. Ros S and Schulze A. Glycolysis back in the limelight: systemic targeting of HK2 blocks tumor growth. Cancer Discov. 2013; 3(10):1105-1107.
173. Cervantes-Madrid D, Romero Y and Duenas-Gonzalez A. Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy. Biomed Res Int. 2015; 2015:690492.
174. Spoden GA, Mazurek S, Morandell D, Bacher N, Ausserlechner MJ, Jansen-Durr P, Eigenbrodt E and Zwerschke W. Isotype-specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation. Int J Cancer. 2008; 123(2):312-321.
175. Calabretta S, Bielli P, Passacantilli I, Pilozzi E, Fendrich V, Capurso G, Fave GD and Sette C. Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells. Oncogene. 2015 Aug 3 doi: 10.1038/onc.2015.270. [Epub ahead of print]
176. Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DS, Thomas CJ, Vander Heiden MG and Cantley LC. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science. 2011; 334(6060):1278-1283.
177. Bluemlein K, Gruning NM, Feichtinger RG, Lehrach H, Kofler B and Ralser M. No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis. Oncotarget. 2011; 2(5):393-400. doi: 10.18632/oncotarget.278.
178. Desai S, Ding M, Wang B, Lu Z, Zhao Q, Shaw K, Yung WK, Weinstein JN, Tan M and Yao J. Tissue-specific isoform switch and DNA hypomethylation of the pyruvate kinase PKM gene in human cancers. Oncotarget. 2014; 5(18):8202-8210. doi: 10.18632/oncotarget.1159.
179. Zhan C, Yan L, Wang L, Ma J, Jiang W, Zhang Y, Shi Y and Wang Q. Isoform switch of pyruvate kinase M1 indeed occurs but not to pyruvate kinase M2 in human tumorigenesis. PLoS One. 2015; 10(3):e0118663.
180. Cortes-Cros M, Hemmerlin C, Ferretti S, Zhang J, Gounarides JS, Yin H, Muller A, Haberkorn A, Chene P, Sellers WR and Hofmann F. M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth. Proc Natl Acad Sci U S A. 2013; 110(2):489-494.
181. Doherty JR, Yang C, Scott KE, Cameron MD, Fallahi M, Li W, Hall MA, Amelio AL, Mishra JK, Li F, Tortosa M, Genau HM, Rounbehler RJ, Lu Y, Dang CV, Kumar KG, et al. Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis. Cancer Res. 2014; 74(3):908-920.
182. Leiblich A, Cross SS, Catto JW, Phillips JT, Leung HY, Hamdy FC and Rehman I. Lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer. Oncogene. 2006; 25(20):2953-2960.
183. Cui J, Quan M, Jiang W, Hu H, Jiao F, Li N, Jin Z, Wang L and Wang Y. Suppressed expression of LDHB promotes pancreatic cancer progression via inducing glycolytic phenotype. Med Oncol. 2015; 32(5):143.
184. Kim JH, Kim EL, Lee YK, Park CB, Kim BW, Wang HJ, Yoon CH, Lee SJ and Yoon G. Decreased lactate dehydrogenase B expression enhances claudin 1-mediated hepatoma cell invasiveness via mitochondrial defects. Exp Cell Res. 2011; 317(8):1108-1118.
185. McCleland ML, Adler AS, Deming L, Cosino E, Lee L, Blackwood EM, Solon M, Tao J, Li L, Shames D, Jackson E, Forrest WF and Firestein R. Lactate dehydrogenase B is required for the growth of KRAS-dependent lung adenocarcinomas. Clin Cancer Res. 2013; 19(4):773-784.
186. Zha X, Wang F, Wang Y, He S, Jing Y, Wu X and Zhang H. Lactate dehydrogenase B is critical for hyperactive mTORmediated tumorigenesis. Cancer Res. 2011; 71(1):13-18.
187. Tambe Y, Hasebe M, Kim CJ, Yamamoto A and Inoue H. The drs tumor suppressor regulates glucose metabolism via lactate dehydrogenase-B. Mol Carcinog. 2015; 55(1):52-63.
188. Zhou Y, Shingu T, Feng L, Chen Z, Ogasawara M, Keating MJ, Kondo S and Huang P. Metabolic alterations in highly tumorigenic glioblastoma cells: preference for hypoxia and high dependency on glycolysis. J Biol Chem. 2011; 286(37):32843-32853.
189. Nakano A, Tsuji D, Miki H, Cui Q, El Sayed SM, Ikegame A, Oda A, Amou H, Nakamura S, Harada T, Fujii S, Kagawa K, Takeuchi K, Sakai A, Ozaki S, Okano K, et al. Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells. PLoS One. 2011; 6(11):e27222.