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Tumorigenesis and Metabolism Disorder

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Abstract

During the tumorigenic process, cancer cells always readjust their metabolism to obtain the energy and metabolites to sustain their increased proliferation. The activation of oncogenes and the loss of tumor suppressors are key molecular events controlling the acquisition of metabolic reprogramming. Many factors can cause the occurrence of metabolic reprogramming in tumor cells, such as changes of tumor microenvironment, activation of oncogenes, and inactivation of tumor suppressor genes. Metabolic pathways such as glycolysis and glutamine metabolism can be altered in tumor cells, thereby making these metabolic pathways adapted to tumor survival and proliferation. These metabolic pathways of tumor cells generate specific metabolites, which have been reported as new clues for cancer treatment. Therefore, signature metabolites in cancers play very important roles in tumor progression and can be used in diagnosis and prognosis of cancers.

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References

  • Abidin AZ, Garassino MC, Califano R, Harle A, Blackhall F (2010) Targeted therapies in small cell lung cancer: a review. Ther Adv Med Oncol 2(1):25–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams S et al (2012) The kynurenine pathway in brain tumor pathogenesis. Cancer Res 72:5649–5657

    Article  CAS  PubMed  Google Scholar 

  • Agostino C et al (2006) Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 101(3):513

    Article  CAS  Google Scholar 

  • Aisen AM, Martel W, Braunstein EM, Mcmillin KI, Phillips WA, Kling TF (1986) MRI and CT evaluation of primary bone and soft-tissue tumors. Year Book Medical Publishers, Chicago

    Book  Google Scholar 

  • Akram M (2013) Mini-review on glycolysis and cancer. J Cancer Educ 28:454–457

    Article  CAS  PubMed  Google Scholar 

  • Ali D et al (2010) Identification of novel epigenetic biomarkers in colorectal cancer, GLDC and PPP1R14A. Eur J Cancer 8:175–175

    Article  Google Scholar 

  • Amelio I et al (2014) Serine and glycine metabolism in cancer. Trends Biochem Sci 39:191–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aronson JK (1999) Biomarkers and surrogate endpoints. Br J Clin Pharmacol 6(4):179

    Google Scholar 

  • Baggetto LG (1992) Deviant energetic metabolism of glycolytic cancer cells. Biochimie 74:959–974

    Article  CAS  PubMed  Google Scholar 

  • Balliet RM et al (2011) Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth. Cell Cycle 10:4065–4073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bao B et al (2011) Anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. PLoS One 6:e17850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barger JF et al (2013) S6K1 determines the metabolic requirements for BCR-ABL survival. Oncogene 32:453–461

    Article  CAS  PubMed  Google Scholar 

  • Bensaad K et al (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126:107–120

    Article  CAS  PubMed  Google Scholar 

  • Berndt B et al (2013) Cell fusion is a potent inducer of aneuploidy and drug resistance in tumor cell normal cell hybrids. Crit Rev Oncog 18:97–113

    Article  PubMed  Google Scholar 

  • Biaglow JE, Miller RA (2005) The thioredoxin reductase/thioredoxin system: novel redox targets for cancer therapy. Cancer Biol Ther 4(1):13–20

    Article  Google Scholar 

  • Blair DG et al (1981) Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. Science 212:941–943

    Article  CAS  PubMed  Google Scholar 

  • Bleeker FE, Lamba S, Leenstra S, Troost D, Hulsebos T, Vandertop WP, Frattini M, Molinari F, Knowles M, Cerrato A (2010) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30(1):7–11

    Article  CAS  Google Scholar 

  • Bobarykina AY, Minchenko DO, Opentanova IL, Moenner M, Caro J, Esumi H, Minchenko OH (2006) Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers. Acta Biochim Pol 53(4):789–799

    CAS  PubMed  Google Scholar 

  • Bonnet S, Archer SL, Allalunisturner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S (2007) A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11(1):37–51

    Article  CAS  PubMed  Google Scholar 

  • Borodovsky A, Seltzer MJ, Riggins GJ (2012) Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2. Curr Opin Oncol 24(1):83–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bralten LB et al (2011) IDH1 R132H decreases proliferation of glioma cell lines in vitro and in vivo. Ann Neurol 69:455–463

    Article  CAS  PubMed  Google Scholar 

  • Branford S et al (2003) Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 102:276–283

    Article  CAS  PubMed  Google Scholar 

  • Buttar NS et al (2014) Aspirin mediated downregulation of Warburg kinase AKT1 in patients with Barrett’s esophagus: implications in neoplastic transformation. Cancer Prev Res 5:PR-03-PR-03

    Google Scholar 

  • Cairns RA et al (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95

    Article  CAS  PubMed  Google Scholar 

  • Calin GA et al (2008) MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A 105:5166–5171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camarero N et al (2006) Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer. Mol Cancer Res 4:645–653

    Article  CAS  PubMed  Google Scholar 

  • Carrola J, Rocha CM, Barros AS, Gil AM, Goodfellow BJ, Carreira IM, Bernardo J, Gomes A, Sousa V, Carvalho L (2011) Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of urine. J Proteome Res 10(1):221

    Article  CAS  PubMed  Google Scholar 

  • Chaffer CL et al (2013) Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 154:61–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaneton B, Gottlieb E (2012) Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem Sci 37:309–316

    Article  CAS  PubMed  Google Scholar 

  • Chang Y et al (2014) AMPK and metabolisms of glucose and lipid. Adv Mater Res 887:547–550

    Article  CAS  Google Scholar 

  • Chen XQ, Stroun M, Anker P (2007) Cancer diagnosis method. USA Patent 7163789

    Google Scholar 

  • Chen Q et al (2015) The transcription factor C-Myc suppresses MiR-23b and MiR-27b transcription during fetal distress and increases the sensitivity of neurons to hypoxia-induced apoptosis. PLoS One 10:e0120217

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen Y, Zhang S, Wang Q, Zhang X (2017) Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein. J Hematol Oncol 10:36. https://doi.org/10.1186/s13045-017-0408-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiavarina B et al (2011) Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth. Cancer Biol Ther 12:1101–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiba T et al (2006) Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 44:240–251

    Article  CAS  PubMed  Google Scholar 

  • Chowdhury R, Yeoh KK, Tian YM, Hillringhaus L, Bagg EA, Rose NR, Leung IKH, Li XS, Woon ECY, Yang M (2011) The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep 12(5):463–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ciavardelli D, Rossi C, Barcaroli D, Volpe S, Consalvo A, Zucchelli M, Cola AD, Scavo E, Carollo R, D’agostino D (2014) Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment. Cell Death Dis 5(7):e1336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cioce M et al (2014) Metformin-induced metabolic reprogramming of chemoresistant ALDH breast cancer cells. Oncotarget 5:4129–4143

    Article  PubMed  PubMed Central  Google Scholar 

  • Clem B, Telang S, Clem A, Yalcin A, Meier J, Simmons A, Rasku MA, Arumugam S, Dean WL, Eaton J (2008) Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Mol Cancer Ther 7(1):110

    Article  CAS  PubMed  Google Scholar 

  • Clem BF, O’neal J, Tapolsky G, Clem AL, Imbert-Fernandez Y, Klarer AC, Redman R, Miller DM, Trent JO (2013) Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol Cancer Ther 12(8):1461–1470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coleman MC et al (2004) Inhibition of glucose metabolism in pancreatic cancer induces cytotoxicity via metabolic oxidative stress. J Am Coll Surg 199:24–24

    Article  Google Scholar 

  • Collier JJ et al (2003) c-Myc is required for the glucose-mediated induction of metabolic enzyme genes. J Biol Chem 278:6588–6595

    Article  CAS  PubMed  Google Scholar 

  • Cory JG, Cory AH (2006) Critical roles of glutamine as nitrogen donors in purine and pyrimidine nucleotide synthesis: asparaginase treatment in childhood acute lymphoblastic leukemia. Vivo 20(5):587–589

    CAS  Google Scholar 

  • Costello LC, Franklin RB (2005) ‘Why do tumour cells glycolyse?’: from glycolysis through citrate to lipogenesis. Mol Cell Biochem 280(1–2):1–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Curry JM et al (2013) Cancer metabolism, stemness and tumor recurrence. Cell Cycle 12:1371–1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dalerba P et al (2007) Cancer Stem cells: models and concepts. Annu Rev Med 58:267–284

    Article  CAS  PubMed  Google Scholar 

  • Dang CV (2010) Rethinking the Warburg effect with Myc micromanaging glutamine metabolism. Cancer Res 70:859–862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dang CV (2013) MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harb Perspect Med 3:341–350

    Article  CAS  Google Scholar 

  • Dang L, White DW, Gross S, Bennett BD, Bittinger MA et al (2010) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462(7274):739–744

    Article  CAS  Google Scholar 

  • Dang L, Yen K, Attar EC (2016) IDH mutations in cancer and progress toward development of targeted therapeutics. Ann Oncol 27(4):599–608

    Article  CAS  PubMed  Google Scholar 

  • Daye D, Wellen KE (2012) Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Semin Cell Dev Biol 23:362–369

    Article  CAS  PubMed  Google Scholar 

  • Dayton TL et al (2016) PKM2, cancer metabolism, and the road ahead. EMBO Rep 17:1721–1730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Demetrius LA et al (2010) Cancer proliferation and therapy: the Warburg effect and quantum metabolism. Theor Biol Med Model 7:2–19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Deshmukh A et al (2016) Cancer stem cell metabolism: a potential target for cancer therapy. Mol Cancer 15(1):69–78

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Di TL et al (2007) Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology 45(3):725–734

    Article  CAS  Google Scholar 

  • Diazruiz R et al (2011) The Warburg and Crabtree effects: on the origin of cancer cell energy metabolism and of yeast glucose repression. Biochim Biophys Acta 1807:568–576

    Article  CAS  Google Scholar 

  • Dong G et al (2016) PKM2 and cancer: the function of PKM2 beyond glycolysis. Oncol Lett 11:1980–1986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eason K, Sadanandam A (2016) Molecular or metabolic reprograming: what triggers tumor subtypes? Cancer Res 76:5195–5200

    Article  CAS  PubMed  Google Scholar 

  • Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV (2014) Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Exp Hematol 42(4):247–251

    Article  CAS  PubMed  Google Scholar 

  • Eng CH, Abraham RT (2011) The autophagy conundrum in cancer: influence of tumorigenic metabolic reprogramming. Oncogene 30:4687–4696

    Article  CAS  PubMed  Google Scholar 

  • Fan J, Kang HB, Shan C, Elf S, Lin R, Xie J, Gu TL, Aguiar M, Lonning S, Chung TW (2011) Tyr-301 phosphorylation inhibits pyruvate dehydrogenase by blocking substrate binding and promotes the Warburg effect. J Biol Chem 289(38):26533

    Article  CAS  Google Scholar 

  • Fantin VR, Stpierre J, Leder P (2006) Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9(6):425–434

    Article  CAS  PubMed  Google Scholar 

  • Fantin VR et al (2010) Cancer-associated metabolite 2-hydroxyglutarate accumulates in AML with IDH1/2 mutations. Cancer Res 70:5452–5452

    Article  Google Scholar 

  • Fathi AT, Sadrzadeh H, Borger DR, Ballen KK, Amrein PC, Attar EC, Foster J, Burke M, Lopez HU, Matulis CR (2012) Prospective serial evaluation of 2-hydroxyglutarate, during treatment of newly diagnosed acute myeloid leukemia, to assess disease activity and therapeutic response. Blood 120(23):4649

    Article  CAS  PubMed  Google Scholar 

  • Fei X et al (2012) MicroRNA-195-5p suppresses glucose uptake and proliferation of human bladder cancer T24 cells by regulating GLUT3 expression. FEBS Lett 586:392–397

    Article  CAS  PubMed  Google Scholar 

  • Ferreira LM et al (2012) Metabolic reprogramming of the tumor. Oncogene 31:3999–4011

    Article  CAS  PubMed  Google Scholar 

  • Fiehn O (2002) Metabolomics--the link between genotypes and phenotypes. Plant Mol Biol 48(2):155–171

    Article  CAS  PubMed  Google Scholar 

  • Flavahan WA, Wu Q, Hitomi M, Rahim N, Kim Y, Sloan AE, Weil RJ, Nakano I, Sarkaria JN, Stringer BW (2013) Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nat Neurosci 16(10):1373–1382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fogarty S, Hardie DG (2010) Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim Biophys Acta Proteins Proteomics 1804:581–591

    Article  CAS  Google Scholar 

  • Fong LY et al (2017) Integration of metabolomics, transcriptomics, and microRNA expression profiling reveals a miR-143-HK2-glucose network underlying zinc-deficiency-associated esophageal neoplasia. Oncotarget 8:81910–81925

    PubMed  PubMed Central  Google Scholar 

  • Fox MP et al (2011) C-Myc overexpression drives aerobic glycolysis independent of anaplerotic pyruvate carboxylase expression in non small cell lung cancer. J Am Coll Surg 213:S39–S39

    Article  Google Scholar 

  • Furuta E et al (2010) Metabolic genes in cancer: their roles in tumor progression and clinical implications. Biochim Biophys Acta Rev Cancer 1805:141–152

    Article  CAS  Google Scholar 

  • Galbiati F et al (2001) Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via a p53/p21WAF1/Cip1-dependent mechanism. Mol Biol Cell 12:2229–2244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galoian K et al (2009) Myc-oncogene inactivating effect by Proline Rich Polypeptide (PRP-1) in chondrosarcoma JJ012 cells. Neurochem Res 34:379–385

    Article  CAS  PubMed  Google Scholar 

  • Galon J et al (2012) Cancer classification using the Immunoscore: a worldwide task force. J Transl Med 10:205–213

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao N et al (2004) G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells. Am J Phys Cell Phys 287:C281

    Article  CAS  Google Scholar 

  • Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K et al (2009) c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458(7239):762–765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao H, Lu Q, Liu X, Cong H, Zhao L, Wang H, Lin D (2010) Application of 1H NMR-based metabonomics in the study of metabolic profiling of human hepatocellular carcinoma and liver cirrhosis. Cancer Sci 100(4):782–785

    Article  CAS  Google Scholar 

  • Garcia E, Andrews C, Hua J, Kim HL, Sukumaran DK, Szyperski T, Odunsi K (2011) Diagnosis of early stage ovarian cancer by 1H NMR metabonomics of serum explored by use of a micro-flow NMR probe. J Proteome Res 10(4):1765–1771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899

    Article  CAS  PubMed  Google Scholar 

  • Gershon TR, Crowther AJ, Andrey T, Idoia G, Ryan A, Yuan H, Ryan MC, Jeffrey M, James O, Mohanish D (2013) Hexokinase-2-mediated aerobic glycolysis is integral to cerebellar neurogenesis and pathogenesis of medulloblastoma. Cancer Metab 1(1):2

    Article  PubMed  PubMed Central  Google Scholar 

  • Gottlieb E, Tomlinson IP (2005) Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 5(11):857–866

    Article  CAS  PubMed  Google Scholar 

  • Gottlob K et al (2001) Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev 15:1406–1418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gottschalk S et al (2004) Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res 10:6661–6668

    Article  CAS  PubMed  Google Scholar 

  • Gowda P et al (2018) Mutant IDH1 disrupts PKM2-β-catenin-BRG1 transcriptional network driven CD47 expression. Mol Cell Biol 38. https://doi.org/10.1128/MCB.00001-18

  • Granchi C et al (2011) Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells. J Med Chem 54:1599–1612

    Article  CAS  PubMed  Google Scholar 

  • Gwak H et al (2015) Cancer-specific interruption of glucose metabolism by resveratrol is mediated through inhibition of Akt/GLUT1 axis in ovarian cancer cells. Mol Carcinog 54(12):1529–1540

    Article  CAS  PubMed  Google Scholar 

  • Hakim M, Billan S, Tisch U, Peng G, Dvrokind I, Marom O, Abdahbortnyak R, Kuten A, Haick H (2011) Diagnosis of head-and-neck cancer from exhaled breath. Br J Cancer 104(10):1649–1655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  • Haynes HR et al (2014) Prognostic and predictive biomarkers in adult and pediatric gliomas: toward personalized treatment. Front Oncol 4:47–59

    Article  PubMed  PubMed Central  Google Scholar 

  • He TL et al (2005) The c-Myc–LDHA axis positively regulates aerobic glycolysis and promotes tumor progression in pancreatic cancer. Med Oncol 32(7):187–202

    Article  CAS  Google Scholar 

  • Hebertchatelain E et al (2012) Preservation of NADH ubiquinone- oxidoreductase activity by Src kinase-mediated phosphorylation of NDUFB10. BBA-Bioenergetics 1817:718–725

    Article  CAS  Google Scholar 

  • Heng B et al (2016) Understanding the role of the kynurenine pathway in human breast cancer immunobiology. Oncotarget 7:6506–6520

    PubMed  Google Scholar 

  • Hensley CT, Wasti AT, Deberardinis RJ (2013) Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Investig 123(9):3678–3684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirsch HA et al (2009) Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res 69:7507–7511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoon H, Xuan YI, Bae KY, Gwang L, Wooyoung S, Yun J, In-Hye H, Han SU (2013) Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol 42(1):44–54

    Article  CAS  Google Scholar 

  • Hresko RC, Hruz PW (2011) HIV protease inhibitors act as competitive inhibitors of the cytoplasmic glucose binding site of GLUTs with differing affinities for GLUT1 and GLUT4. PLoS One 6(9):e25237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu ZY et al (2014) Glycolytic genes in cancer cells are more than glucose metabolic regulators. J Mol Med 92:1009–1009

    Article  Google Scholar 

  • Huang R et al (2017) Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124–2HG. Autophagy 13:1–20

    Article  CAS  Google Scholar 

  • Ibsen KH (1961) The Crabtree effect: a review. Cancer Res 21(21):829

    CAS  PubMed  Google Scholar 

  • Jaekyoung S, Lyssiotis CA, Ying H, Wang X, Hua S, Matteo L, Perera RM, Ferrone CR, Edouard M, Ng SC (2013) Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway. Nature 496(7443):101–105

    Article  CAS  Google Scholar 

  • Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, Kafri R, Kirschner MW, Clish CB, Mootha VK (2012) Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336(6084):1040–1044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jha MK, Suk K (2013) Pyruvate dehydrogenase kinase as a potential therapeutic target for malignant gliomas. Brain Tumor Res Treat 1(2):57–63

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang W et al (2015) FOXM1-LDHA signaling promoted gastric cancer glycolytic phenotype and progression. Int J Clin Exp Pathol 8:6756–6763

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jing L et al (2017) Induced-decay of glycine decarboxylase transcripts as an anticancer therapeutic strategy for non-small-cell lung carcinoma. Mol Ther Nucleic Acids 9:263–273

    Article  CAS  Google Scholar 

  • Jobard E, Pontoizeau C, Blaise BJ, Bachelot T, Trédan O (2014) A serum nuclear magnetic resonance-based metabolomic signature of advanced metastatic human breast cancer. Cancer Lett 343(1):33–41

    Article  CAS  PubMed  Google Scholar 

  • Jones RG, Thompson CB (2009) Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 23(5):537–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung SY, Jeon HK, Choi JS, Kim YJ (2012) Reduced expression of FASN through SREBP-1 down-regulation is responsible for hypoxic cell death in HepG2 cells. J Cell Biochem 113(12):3730–3739

    Article  CAS  PubMed  Google Scholar 

  • Kang MR, Kim MS, Oh JE, Kim YR, Song SY, Seo SI, Lee JY, Yoo NJ, Lee SH (2010) Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer 125(2):353–355

    Article  CAS  Google Scholar 

  • Kapiteijn E et al (2001) Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol 195:171–178

    Article  CAS  PubMed  Google Scholar 

  • Keller KE et al (2014) SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells. Mol Cell 53:700–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JW et al (2007) Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol 27:7381–7393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kinzler KW (1998) ONCOGENESIS: landscaping the cancer terrain. Science 280:1036–1037

    Article  CAS  PubMed  Google Scholar 

  • Klepper J, Voit T (2002) Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-- a review. Eur J Pediatr 161(6):295–304

    Article  CAS  PubMed  Google Scholar 

  • Koseki J et al (2015) Mathematical analysis predicts imbalanced IDH1/2 expression associates with 2-HG-inactivating Î2-oxygenation pathway in colorectal cancer. Int J Oncol 46:1181–1191

    Article  CAS  PubMed  Google Scholar 

  • Koster R et al (2017) Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients. Int J Cancer 142:1594–1601

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Koukourakis MI, Giatromanolaki A, Simopoulos C, Polychronidis A, Sivridis E (2005) Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer. Clin Exp Metastasis 22(1):25–30

    Article  CAS  PubMed  Google Scholar 

  • Kubo Y et al (2014) Molecular tumorigenesis of the skin. J Med Investig 61:7–14

    Article  Google Scholar 

  • Kubota Y et al (1987) The enhanced 32P labeling of CDP-diacylglycerol in c-myc gene expressed human kidney cancer cells. FEBS Lett 212:159–162

    Article  CAS  PubMed  Google Scholar 

  • Kumar B, Bamezai RNK (2015) Moderate DNA damage promotes metabolic flux into PPP via PKM2 Y-105 phosphorylation: a feature that favours cancer cells. Mol Biol Rep 42:1317–1321

    Article  CAS  PubMed  Google Scholar 

  • Latham T et al (2012) Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression. Nucleic Acids Res 40:4794–4803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le MT et al (2009) MicroRNA-125b is a novel negative regulator of p53. Genes Dev 23:862–876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H (2012) Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B-cells. Cell Metab 15(1):110–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee EK et al (2010) Transgelin promotes migration and invasion of cancer stem cells. J Proteome Res 9:5108–5117

    Article  CAS  PubMed  Google Scholar 

  • Lee JEA et al (2014) MYC function and regulation in flies: how Drosophila has enlightened MYC cancer biology. Aims Energy 1:81–98

    Google Scholar 

  • Leerapun A et al (2007) The utility of AFP-L3% in the diagnosis of hepatocellular carcinoma: evaluation in a US referral population. Clinical Gastroenterology & Hepatology 5(3):267–267

    Article  Google Scholar 

  • Levine AJ, Puzio-Kuter AM (2010) The control of the metabolic switch in cancersbyoncogenes and tumor suppressor genes. Science 330:1340–1344

    Article  CAS  PubMed  Google Scholar 

  • Li C et al (2006) Identification of pancreatic cancer stem cells. J Surg Res 130:194–195

    Google Scholar 

  • Li W et al (2016) Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway. Exp Cell Res 349:320–327

    Article  CAS  PubMed  Google Scholar 

  • Liang Q, Yu Q, Wu H, Zhu Y, Zhang A (2014) Metabolite fingerprint analysis of cervical cancer using LC-QTOF/MS and multivariate data analysis. Anal Methods 6(12):3937–3942

    Article  CAS  Google Scholar 

  • Liao Y (2014) Akt signaling pathway in the regulation of glucose metabolism in cancer cells. Electron J Metab Nutr Cancer 1(3):61–69

    Google Scholar 

  • Liberti MV, Locasale JW (2016) The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 41:211–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ligor T, Szeliga J, Jackowski M, Buszewski B (2007) Preliminary study of volatile organic compounds from breath and stomach tissue by means of solid phase microextraction and gas chromatography-mass spectrometry. J Breath Res 1(1):016001

    Article  CAS  PubMed  Google Scholar 

  • Lin B, Xu LI, Zhang H (2015) Potential therapeutic target of energy metabolism for cancer. Chem Life 35(1):45–50

    Google Scholar 

  • Lin CP et al (2012) The emerging functions of the p53-miRNA network in stem cell biology. Cell Cycle 11:2063–2072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lincet H, Icard P (2014) How do glycolytic enzymes favour cancer cell proliferation by nonmetabolic functions? Oncogene 34:3751–3759

    Article  PubMed  CAS  Google Scholar 

  • Liu YC et al (2008) Global regulation of nucleotide biosynthetic genes by c-Myc. PLoS One 3:e2722

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu T, Kishton RJ, Macintyre AN, Gerriets VA, Xiang H, Liu X, Abel ED, Rizzieri D, Locasale JW, Rathmell JC (2014) Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis. Cell Death Dis 5(11):e1470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu F et al (2017) PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis. Nat Cell Biol 19:1358–1370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Q, Huang Q (2015) Characteristics of energy metabolism of tumor cells and its significance. Chem Life 35(3):387–391

    Google Scholar 

  • Lock R et al (2011) Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell 22:165–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loiseau AM, Rousseau GG, Hue L (1985) Fructose 2,6-bisphosphate and the control of glycolysis by glucocorticoids and by other agents in rat hepatoma cells. Cancer Res 45(9):4263–4269

    CAS  PubMed  Google Scholar 

  • Lopiccolo J et al (2008) Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat 11:32–50

    Article  CAS  PubMed  Google Scholar 

  • Lu H et al (2010) MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism. Cardiovasc Res 86:410–420

    Article  CAS  PubMed  Google Scholar 

  • Lunt SY et al (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27:441–464

    Article  CAS  PubMed  Google Scholar 

  • Macheda ML et al (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202:654–662

    Article  CAS  PubMed  Google Scholar 

  • Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP (2014) The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab 20(1):61–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malik ST et al (1991) Antitumor activity of γ-interferon in ascitic and solid tumor models of human ovarian cancer. Cancer Res 51:6643–6649

    CAS  PubMed  Google Scholar 

  • Manerba M, Vettraino M, Fiume L, Sartini A, Giacomini E, Buonfiglio R, Roberti M, Recanatini M (2012) Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase. ChemMedChem 7(2):311–317

    Article  CAS  PubMed  Google Scholar 

  • Mao Y et al (2010) Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut 59(12):1687–1693

    Article  CAS  PubMed  Google Scholar 

  • Mardis ER, Ding L, Dooling DJ, Larson DE, Mclellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, Mcgrath SD (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361(11):1058–1066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marín-Hernández A et al (2011) Modeling cancer glycolysis. Biochim Biophys Acta (BBA) – Bioenergetics 1807:755–767

    Article  CAS  Google Scholar 

  • Marrero JA et al (2005) GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 43(6):1007–1012

    Article  CAS  PubMed  Google Scholar 

  • Martinezoutschoorn UE et al (2011) Ketones and lactate increase cancer cell “stemness,” driving recurrence, metastasis and poor clinical outcome in breast cancer: achieving personalized medicine via Metabolo-Genomics. Cell Cycle 10:1271–1286

    Article  CAS  Google Scholar 

  • Mathews EH, Liebenberg L (2013) Is knowledge of brain metabolism the key to treatinghighly glycolytic cancers and metastases? Neuro-Oncology 15:649–649

    Article  PubMed  PubMed Central  Google Scholar 

  • Mathews EH et al (2011) High-glycolytic cancers and their interplay with the body’s glucose demand and supply cycle. Med Hypotheses 76:157–165

    Article  CAS  PubMed  Google Scholar 

  • Mcbrayer SK, Cheng JC, Singhal S, Krett NL, Rosen ST, Shanmugam M (2012) Multiple myeloma exhibits novel dependence on GLUT4, GLUT8, and GLUT11: implications for glucose transporter-directed therapy. Blood 119(20):4686–4697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mccartan D et al (2012) Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER-independent mediator of endocrine resistant breast cancer. Cancer Res 72:220–229

    Article  CAS  PubMed  Google Scholar 

  • Meadows AL et al (2008) Metabolic and morphological differences between rapidly proliferating cancerous and normal breast epithelial cells. Biotechnol Prog 24:334–341

    Article  CAS  PubMed  Google Scholar 

  • Mennigen JA (2016) Micromanaging metabolism-a role for miRNAs in teleost energy metabolism. Comp Biochem Physiol 199:115–125

    Article  CAS  Google Scholar 

  • Mentis AF, Kararizou E (2010) Metabolism and cancer: an up-to-date review of a mutual connection. Asian Pac J Cancer Prev 11(6):1437

    PubMed  Google Scholar 

  • Migneco G et al (2010) Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: evidence for stromal-epithelial metabolic coupling. Cell Cycle 9:2412–2422

    Article  CAS  PubMed  Google Scholar 

  • Min HY, Lee HY (2018) Oncogene-driven metabolic alterations in cancer. Biomol Ther 26:45–56

    Article  CAS  Google Scholar 

  • Min HL et al (2016) Epigenetic silencing of the putative tumor suppressor gene GLDC (Glycine Dehydrogenase) in gastric carcinoma. Anticancer Res 36:179–187

    CAS  PubMed  Google Scholar 

  • Miyahara T et al (2007) Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs. Am J Physiol Lung Cell Mol Physiol 293:11–21

    Article  CAS  Google Scholar 

  • Morrish F et al (2010) Myc-dependent mitochondrial generation of acetyl-CoA contributes to fatty acid biosynthesis and histone acetylation during cell cycle entry. J Biol Chem 285:36267–36274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Münger K et al (2004) Mechanisms of human papillomavirus-induced oncogenesis. J Virol 78:11451–11460

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murray GI et al (1993) Expression of xenobiotic metabolizing enzymes in breast cancer. J Pathol 169:347–353

    Article  CAS  PubMed  Google Scholar 

  • Narahara K, Kimura S, Kikkawa K, Takahashi Y, Wakita Y, Kasai R, Nagai S, Nishibayashi Y, Kimoto H (1985) Probable assignment of soluble isocitrate dehydrogenase (IDH1) to 2q33.3. Hum Genet 71(1):37

    Article  CAS  PubMed  Google Scholar 

  • Neiff N, Dhliwayo T, Suarez EA, Burgueno J, Trachsel S (2010) Advances in research of anti-tumor treatment with natural killer cells. J Chin PLA Postgrad Med Sch 29(6):669–690

    Google Scholar 

  • Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136(3):521–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noh S et al (2014) Expression levels of serine/glycine metabolism-related proteins in triple negative breast cancer tissues. Tumour Biol 35:4457–4468

    Article  CAS  PubMed  Google Scholar 

  • Oermann EK et al (2012) Alterations of metabolic genes and metabolites in cancer. Semin Cell Dev Biol 23:370–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oh IU, Inazawa J, Kim YO, Song BJ, Huh TL (1996) Assignment of the human mitochondrial NADP + -specific isocitrate dehydrogenase (IDH2) gene to 15q26.1 by in situ hybridization. Genomics 38(1):104–106

    Article  CAS  PubMed  Google Scholar 

  • Ono K (2011) MicroRNA links obesity and impaired glucose metabolism. Cell Res 21:864–866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ono M et al (1990) Measurement of immunoreactive prothrombin precursor and vitamin-Kdependent gamma-carboxylation in human hepatocellular carcinoma tissues: decreased carboxylation of prothrombin precursor as a cause of des-gamma-carboxyprothrombin synthesis. Tumour Biol 11(6):319–326

    Article  CAS  PubMed  Google Scholar 

  • Pai YJ et al (2015) Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. Nat Commun 6:6388–6399

    Article  CAS  PubMed  Google Scholar 

  • Painter RB, Hughes WL (2010) Nucleic acid metabolism and the lethal effect of radiation on cultured human cells (HeLa). Ann N Y Acad Sci 95:960–968

    Article  Google Scholar 

  • Patra KC, Wang Q, Bhaskar PT, Miller L, Wang Z, Wheaton W, Chandel N, Laakso M, Muller WJ, Allen EL (2013) Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell 24(2):213–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peirispagès M et al (2016) Cancer stem cell metabolism. Breast Cancer Res 18:55–64

    Article  CAS  Google Scholar 

  • Peng G, Hakim M, Broza YY, Billan S, Abdah-Bortnyak R, Kuten A, Tisch U, Haick H (2010) Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br J Cancer 103(4):542–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phillips M, Cataneo RN, Saunders C, Hope P, Schmitt P, Wai J (2010) Volatile biomarkers in the breath of women with breast cancer. J Breath Res 4(2):026003

    Article  PubMed  CAS  Google Scholar 

  • Pollard P, Wortham N, Tomlinson I (2003) The TCA cycle and tumorigenesis: the examples of fumarate hydratase and succinate dehydrogenase. Ann Med 35(8):634–635

    Article  CAS  Google Scholar 

  • Prasad N et al (2008) Crosstalk between metabolic and oncogenic pathways via SHIP2 inositol phosphatase. Cancer Res 68:68–78

    Google Scholar 

  • Qing G, Li B, Vu A, Skuli N, Walton Z, Liu X, Mayes P, Wise D, Thompson C, Maris J (2012) ATF4 regulates MYC -mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 22(5):631–644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raimundo N, Baysal BE, Shadel GS (2011) Revisiting the TCA cycle: signaling to tumor formation. Trends Mol Med 17(11):641–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Resende C et al (2010) Genetic and epigenetic alteration in gastric carcinogenesis. Helicobacter 15:34–39

    Article  CAS  PubMed  Google Scholar 

  • Ristow M (2006) Oxidative metabolism in cancer growth. Curr Opin Clin Nutr Metab Care 9:339–345

    Article  CAS  PubMed  Google Scholar 

  • Robb MA, Mcinnes PM, Califf RM (2016) Biomarkers and surrogate endpoints. JAMA 315(11):1107–1108

    Article  CAS  PubMed  Google Scholar 

  • Rosko JE (2006) From adult stem cells to cancer stem cells: Oct-4 Gene, cell-cell communication, and hormones during tumor promotion. Ann N Y Acad Sci 1089:36–58

    Article  CAS  Google Scholar 

  • Ross CD, Gomaa MA, Gillies E, Juengel R, Medina JE (2000) Tumor grade, microvessel density, and activities of malate dehydrogenase, lactate dehydrogenase, and hexokinase in squamous cell carcinoma. Otolaryngology--head and neck surgery. Off J Am Acad Otolaryngol-Head Neck Surg 122(2):195

    Article  CAS  Google Scholar 

  • Sahra IB et al (2010) The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells. Autophagy 6:670–671

    Article  PubMed  Google Scholar 

  • Sampson VB et al (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 67:9762–9770

    Article  CAS  PubMed  Google Scholar 

  • Sanyal S et al (2004) Polymorphisms in DNA repair and metabolic genes in bladder cancer. Carcinogenesis 25:729–734

    Article  CAS  PubMed  Google Scholar 

  • Sasaki M et al (2012) IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature 488:656–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sciacovelli M et al (2014) The metabolic alterations of cancer cells. Methods Enzymol 542:1–23

    Article  CAS  PubMed  Google Scholar 

  • Sebastian C (2014) Tracking down the origin of cancer: metabolic reprogramming as a driver of stemness and tumorigenesis. Crit Rev Oncog 19:363–382

    Article  PubMed  Google Scholar 

  • Sedwick C (2015) Glycolytic cancer cells splice their way out of trouble. J Cell Biol 210:1037–1037

    Article  PubMed Central  Google Scholar 

  • Semenza GL (2008) Tumor metabolism: cancer cells give and take lactate. J Clin Investig 118:3835–3837

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shah M, Allegrucci C (2013) Stem cell plasticity in development and cancer: epigenetic origin of cancer stem cells. Subcell Biochem 61(7):545–565

    Article  CAS  PubMed  Google Scholar 

  • Shariff MIF, Gomaa AI, Cox IJ, Patel M, Williams HRT, Crossey MME, Thillainayagam AV, Thomas HC, Waked I, Khan SA (2011) Urinary metabolic biomarkers of hepatocellular carcinoma in an Egyptian population: a validation study. J Proteome Res 10(4):1828–1836

    Article  CAS  PubMed  Google Scholar 

  • Shaw RJ (2006) Glucose metabolism and cancer. Curr Opin Cell Biol 18:598–608

    Article  CAS  PubMed  Google Scholar 

  • Shen YC, Ou DL, Hsu C, Lin KL, Chang CY, Lin CY, Liu SH, Cheng AL (2013) Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma. Br J Cancer 108(1):72–81

    Article  CAS  PubMed  Google Scholar 

  • Shieh GS et al (2016) Lactate promoting cancer stem cell phenotype and inducing epithelial-mesenchymal transition. Urol Sci 27:S2–S3

    Article  Google Scholar 

  • Shoemaker RH (2006) The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer 6(10):813

    Article  CAS  PubMed  Google Scholar 

  • Shroff EH et al (2015) MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc Natl Acad Sci U S A 112:6539–6544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh SK et al (2004) Cancer stem cells in nervous system tumors. Oncogene 23:7267–7273

    Article  CAS  PubMed  Google Scholar 

  • Smith TA (2000) Mammalian hexokinases and their abnormal expression in cancer. Br J Biomed Sci 57(2):170–178

    CAS  PubMed  Google Scholar 

  • Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyhchang N (2013) Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway. Nature 496(7443):101–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RT, Li Y (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457(7231):910–914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srivastava NK, Pradhan S, Gowda GAN, Kumar R (2010) In vitro, high-resolution 1H and 31P NMR based analysis of the lipid components in the tissue, serum, and CSF of the patients with primary brain tumors: one possible diagnostic view. NMR Biomed 23(2):113–122

    CAS  PubMed  Google Scholar 

  • Stacpoole PW, Nagaraja NV, Hutson AD (2003) Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol 43(7):683–691

    Article  CAS  PubMed  Google Scholar 

  • Stratton MR (2011) Exploring the genomes of cancer cells: progress and promise. Science 331:1553–1558

    Article  CAS  PubMed  Google Scholar 

  • Strimbu K, Tavel JA (2010) What are biomarkers? Curr Opin HIV AIDS 5(6):463–466

    Article  PubMed  PubMed Central  Google Scholar 

  • Suzuki Y et al (2010) Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer. Lung Cancer 67:361–365

    Article  PubMed  Google Scholar 

  • Tabin CJ et al (1982) Mechanism of activation of a human oncogene. Nature 300:143–149

    Article  CAS  PubMed  Google Scholar 

  • Takahiro H et al (2009) MicroRNA-133 regulates the expression of CPT-1b and GLUT4 by targeting SRF and KLF15 and is involved in metabolic control in cardiac myocytes. Biochem Biophys Res Commun 389:315–320

    Article  CAS  Google Scholar 

  • Tao T et al (2014) Loss of SNAIL inhibits cellular growth and metabolism through the miR-128-mediated RPS6KB1/HIF-1α/PKM2 signaling pathway in prostate cancer cells. Tumor Biol 35:8543–8550

    Article  CAS  Google Scholar 

  • Telang S, Yalcin A, Clem AL, Bucala R, Lane AN, Eaton JW, Chesney J (2006) Ras transformation requires metabolic control by 6-phosphofructo-2-kinase. Oncogene 25(55):7225–7234

    Article  CAS  PubMed  Google Scholar 

  • Terunuma A et al (2014) MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis. J Clin Investig 124:398–412

    Article  CAS  PubMed  Google Scholar 

  • Valencia T et al (2014) Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis. Cancer Cell 26:121–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Lith SA et al (2016) Identification of a novel inactivating mutation in Isocitrate Dehydrogenase 1 (IDH1-R314C) in a high grade astrocytoma. Sci Rep 6:30486–30494

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vetter ML, Bishop JM (1988) Cellular ras activity and phospholipid metabolism. Cell 52:63–71

    Article  Google Scholar 

  • Vincent A, Van SI (2012) On the epigenetic origin of cancer stem cells. Biochim Biophys Acta 1826:83–88

    CAS  PubMed  Google Scholar 

  • Walczak K et al (2011) Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells. Scand J Gastroenterol 46:903–912

    Article  CAS  PubMed  Google Scholar 

  • Wang T et al (1976) Aerobic glycolysis during lymphocyte proliferation. Nature 261:702–705

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Travins J, Delabarre B, Penardlacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C (2013a) Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science 340(6132):622–626

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Tiffen J, Bailey CG, Lehman ML, Ritchie W, Fazli L, Metierre C, Feng Y, Li E, Gleave M (2013b) Targeting amino acid transport in metastatic castration-resistant prostate cancer: effects on cell cycle, cell growth, and tumor development. J Natl Cancer Inst 105(19):1463–1473

    Article  CAS  PubMed  Google Scholar 

  • Wang HJ et al (2014) JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. Proc Natl Acad Sci U S A 111:279–284

    Article  CAS  PubMed  Google Scholar 

  • Wanka C et al (2012) Synthesis of cytochrome C oxidase 2: a p53-dependent metabolic regulator that promotes respiratory function and protects glioma and colon cancer cells from hypoxia-induced cell death. Oncogene 31:3764–3776

    Article  CAS  PubMed  Google Scholar 

  • Warburg O (1956) On the origin of cancer cells. Science 123(3191):309–314

    Article  CAS  PubMed  Google Scholar 

  • Warburg et al (1927) The metabolism of tumors in the body. J Gen Physiol 8:519–530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ward PS, Patel J, Wise DR, Abdelwahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzymatic activity that converts α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17(3):225–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warner SL et al (2014) Activators of PKM2 in cancer metabolism. Future Med Chem 6:1167–1178

    Article  CAS  PubMed  Google Scholar 

  • Waterhouse C (2015) Lactate metabolism in patients with cancer. Cancer 33:66–71

    Article  Google Scholar 

  • Weinberg F et al (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A 107:8788–8793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wen CZ, Bing L (2014) Targeting metabolic enzyme with locked nucleic acids in non-small cell lung cancer. Cancer Res 74:1438–1438

    Article  Google Scholar 

  • Wigley WC, Nakashima RA (1992) Evidence for multiple genes coding for the isozymes of hexokinase in the highly glycolytic AS-30D rat hepatoma. FEBS Lett 300:153–156

    Article  CAS  PubMed  Google Scholar 

  • Wong N et al (2015) PKM2 contributes to cancer metabolism. Cancer Lett 356:184–191

    Article  CAS  PubMed  Google Scholar 

  • Woo CC et al (2018) Inhibiting glycine decarboxylase suppresses pyruvate-to-lactate metabolism in lung cancer cells. Front Oncol 8:1–12

    Article  Google Scholar 

  • Wu XZ (2008) Origin of cancer stem cells: the role of self-renewal and differentiation. Ann Surg Oncol 15:407–414

    Article  PubMed  Google Scholar 

  • Xie X et al (2018) Diallyl disulfide inhibits breast cancer stem cell progression and glucose metabolism by targeting CD44/PKM2/AMPK signaling. Curr Cancer Drug Targets 18:592–599

    Article  CAS  PubMed  Google Scholar 

  • Xu RH et al (2005) Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res 65:613–621

    CAS  PubMed  Google Scholar 

  • Xu W, Yang H, Liu Y, Yang Y, Wang P et al (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 19(1):17–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang W et al (2011) Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 480:118–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang W et al (2012a) PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 150:685–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang W et al (2012b) ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol 14:1295–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang X et al (2015) A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis. Tumor Biol 36:383–391

    Article  CAS  Google Scholar 

  • Yang G et al (2016) miR-100 antagonism triggers apoptosis by inhibiting ubiquitination-mediated p53 degradation. Oncogene 36:1023–1037

    Article  PubMed  CAS  Google Scholar 

  • Yang L et al (2017) Glutaminolysis: a hallmark of cancer metabolism. Annu Rev Biomed Eng 19:163–167

    Article  CAS  PubMed  Google Scholar 

  • Ye J et al (2012) Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc Natl Acad Sci U S A 109:6904–6909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yi L, Cao Y, Zhang W, Bergmeier S, Qian Y, Akbar H, Colvin R, Ding J, Tong L, Wu S (2012) 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 11(8):1672–1682

    Article  CAS  Google Scholar 

  • Yi M et al (2013) Metabolic reprogramming in cancer: the art of balance. J Cent South Univ 38:1177–1187

    CAS  Google Scholar 

  • Young VR (1977) Energy metabolism and requirements in the cancer patient. Cancer Res 37:2336–2336

    CAS  PubMed  Google Scholar 

  • Zhang H et al (2007) HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11:407–420

    Article  CAS  PubMed  Google Scholar 

  • Zhang WC et al (2012a) Glycinedecarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell 148:259–272

    Article  CAS  PubMed  Google Scholar 

  • Zhang G et al (2012b) Induced pluripotent stem cell consensus genes: implication for the risk of tumorigenesis and cancers in induced pluripotent stem cell therapy. Stem Cells Dev 21:955–964

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Yang JM (2013) Altered energy metabolism in cancer: a unique opportunity for therapeutic intervention. Cancer Biol Ther 14(2):81–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang F, Zhang Y, Zhao W, Deng K, Wang Z, Yang C, Ma L, Openkova MS, Hou Y, Li K (2017) Metabolomics for biomarker discovery in the diagnosis, prognosis, survival and recurrence of colorectal cancer: a systematic review. Oncotarget 8(21):35460–35472

    PubMed  PubMed Central  Google Scholar 

  • Zheng J (2012) Energy metabolism of cancer: glycolysis versus oxidative phosphorylation. Oncol Lett 4:1151–1157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong W et al (2015) Oxysterol-binding protein-related protein 8 (ORP8) increases sensitivity of hepatocellular carcinoma cells to Fas-mediated apoptosis. J Biol Chem 290:8876–8887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y et al (2012) Golgi protein 73 versus alpha-fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta- analysis. BMC Cancer 12(1):17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Yang, F., Shu, L., Zhang, X. (2019). Tumorigenesis and Metabolism Disorder. In: Zhang, X. (eds) Virus Infection and Tumorigenesis. Springer, Singapore. https://doi.org/10.1007/978-981-13-6198-2_7

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