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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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October 2014 Volume 45 Issue 4

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Review

Clinical impact of the Warburg effect in gastrointestinal cancer (Review)

  • Authors:
    • Hiroshi Sawayama
    • Takatsugu Ishimoto
    • Hidetaka Sugihara
    • Nobutomo Miyanari
    • Yuji Miyamoto
    • Yoshifumi Baba
    • Naoya Yoshida
    • Hideo Baba
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan, Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto 860-0008, Japan
  • Pages: 1345-1354
    |
    Published online on: July 25, 2014
       https://doi.org/10.3892/ijo.2014.2563
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Abstract

Cancer cells exhibit altered glucose metabolism, termed the Warburg effect, which is described by the increased uptake of glucose and the conversion of glucose to lactate in cancer cells under adequate oxygen tension. Recent genetic and metabolic analyses have provided insights into the molecular mechanisms of genes that are involved in the Warburg effect and tumorigenesis. The aim of this review was to discuss significant molecular insights into clinical impacts of the Warburg effect such as oncogenic alterations and overexpression of transcriptional factors (c-Myc and hypoxia-inducible factor), metabolite transporters (glucose transporters) and glycolytic enzymes (hexokinases 2, pyruvate kinase M2, pyruvate dehydrogenase kinase, isozyme 1, lactate dehydrogenase A). Overexpression of transcriptional factors, metabolite transporters and glycolytic enzymes was associated with poor prognosis and may be associated with chemoradiotherapy resistance in multiple gastrointestinal cancer cell types. Novel small molecules targeting these enzymes or transporters exert anti-proliferative effects. Glycolytic enzymes and metabolite transporters may be significant biomarkers for predicting cancer prognosis and may be therapeutic targets in gastrointestinal cancer.
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1 

Warburg O: On respiratory impairment in cancer cells. Science. 124:269–270. 1956.PubMed/NCBI

2 

Younes M, Lechago LV, Somoano JR, Mosharaf M and Lechago J: Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers. Cancer Res. 56:1164–1167. 1996.PubMed/NCBI

3 

Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI

4 

Plathow C and Weber WA: Tumor cell metabolism imaging. J Nucl Med. 49(Suppl 2): S43–S63. 2008. View Article : Google Scholar

5 

Plas DR and Thompson CB: Akt-dependent transformation: there is more to growth than just surviving. Oncogene. 24:7435–7442. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Elstrom RL, Bauer DE, Buzzai M, et al: Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64:3892–3899. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Vousden KH and Ryan KM: p53 and metabolism. Nat Rev Cancer. 9:691–700. 2009. View Article : Google Scholar

8 

Stambolic V, MacPherson D, Sas D, et al: Regulation of PTEN transcription by p53. Mol Cell. 8:317–325. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Jones RG, Plas DR, Kubek S, et al: AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell. 18:283–293. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Shackelford DB and Shaw RJ: The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 9:563–575. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Lu H, Forbes RA and Verma A: Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem. 277:23111–23115. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Zhong H, De Marzo AM, Laughner E, et al: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI

13 

Talks KL, Turley H, Gatter KC, et al: The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol. 157:411–421. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Matsuyama T, Nakanishi K, Hayashi T, et al: Expression of hypoxia-inducible factor-1alpha in esophageal squamous cell carcinoma. Cancer Sci. 96:176–182. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Ogane N, Yasuda M, Shimizu M, et al: Clinicopathological implications of expressions of hypoxia-related molecules in esophageal superficial squamous cell carcinoma. Ann Diagn Pathol. 14:23–29. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Zhang ZG, Zhang QN, Wang XH and Tian JH: Hypoxia-inducible factor 1 alpha (HIF-1alpha) as a prognostic indicator in patients with gastric tumors: a meta-analysis. Asian Pac J Cancer Prev. 14:4195–4198. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Lin S, Ma R, Zheng XY, et al: Meta-analysis of immunohistochemical expression of hypoxia inducible factor-1alpha as a prognostic role in gastric cancer. World J Gastroenterol. 20:1107–1113. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Baba Y, Nosho K, Shima K, et al: HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am J Pathol. 176:2292–2301. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Zheng SS, Chen XH, Yin X and Zhang BH: Prognostic significance of HIF-1alpha expression in hepatocellular carcinoma: a meta-analysis. PloS One. 8:e657532013. View Article : Google Scholar : PubMed/NCBI

20 

Nakamura J, Kitajima Y, Kai K, et al: Hypoxia-inducible factor-1alpha expression predicts the response to 5-fluorouracil-based adjuvant chemotherapy in advanced gastric cancer. Oncol Rep. 22:693–699. 2009.

21 

Nakamura J, Kitajima Y, Kai K, et al: HIF-1alpha is an unfavorable determinant of relapse in gastric cancer patients who underwent curative surgery followed by adjuvant 5-FU chemotherapy. Int J Cancer. 127:1158–1171. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Griffiths EA, Pritchard SA, McGrath SM, et al: Hypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis. Br J Cancer. 98:965–973. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Rasheed S, Harris AL, Tekkis PP, et al: Hypoxia-inducible factor-1alpha and -2alpha are expressed in most rectal cancers but only hypoxia-inducible factor-1alpha is associated with prognosis. Br J Cancer. 100:1666–1673. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Dang CV, Le A and Gao P: MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res. 15:6479–6483. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Calcagno DQ, Leal MF, Assumpcao PP, Smith MA and Burbano RR: MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol. 14:5962–5968. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Liu Y, Gong LP, Dong XL and Liu HG: Detection of C-MYC oncogene translocation and copy number change in the normal-dysplasia- carcinoma sequence of the larynx by fluorescence in situ hybridization. Diagn Cytopathol. 41:515–519. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Tuupanen S, Yan J, Turunen M, et al: Characterization of the colorectal cancer-associated enhancer MYC-335 at 8q24: the role of rs67491583. Cancer Genet. 205:25–33. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Amente S, Lania L and Majello B: Epigenetic reprogramming of Myc target genes. Am J Cancer Res. 1:413–418. 2011.PubMed/NCBI

29 

de Souza CR, Leal MF, Calcagno DQ, et al: MYC deregulation in gastric cancer and its clinicopathological implications. PloS One. 8:e644202013.PubMed/NCBI

30 

He C, Jiang H, Geng S, et al: Expression and prognostic value of c-Myc and Fas (CD95/APO1) in patients with pancreatic cancer. Int J Clin Exp Pathol. 7:742–750. 2014.PubMed/NCBI

31 

Mueckler M, Caruso C, Baldwin SA, et al: Sequence and structure of a human glucose transporter. Science. 229:941–945. 1985. View Article : Google Scholar : PubMed/NCBI

32 

Joost HG and Thorens B: The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review). Mol Membr Biol. 18:247–256. 2001. View Article : Google Scholar

33 

Younes M, Lechago LV, Somoano JR, Mosharaf M and Lechago J: Immunohistochemical detection of Glut3 in human tumors and normal tissues. Anticancer Res. 17:2747–2750. 1997.PubMed/NCBI

34 

Ayala FR, Rocha RM, Carvalho KC, et al: GLUT1 and GLUT3 as potential prognostic markers for oral squamous cell carcinoma. Molecules. 15:2374–2387. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Fonteyne P, Casneuf V, Pauwels P, et al: Expression of hexokinases and glucose transporters in treated and untreated oesophageal adenocarcinoma. Histol Histopathol. 24:971–977. 2009.PubMed/NCBI

36 

Carvalho KC, Cunha IW, Rocha RM, et al: GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker. Clinics (Sao Paulo). 66:965–972. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Griffiths EA, Pritchard SA, Welch IM, Price PM and West CM: Is the hypoxia-inducible factor pathway important in gastric cancer? Eur J Cancer. 41:2792–2805. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Yun J, Rago C, Cheong I, et al: Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 325:1555–1559. 2009. View Article : Google Scholar : PubMed/NCBI

39 

Kawada K, Nakamoto Y, Kawada M, et al: Relationship between 18F-fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer. Clin Cancer Res. 18:1696–1703. 2012.

40 

Yang W, Zheng Y, Xia Y, et al: ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol. 14:1295–1304. 2012. View Article : Google Scholar : PubMed/NCBI

41 

Young CD, Lewis AS, Rudolph MC, et al: Modulation of glucose transporter 1 (GLUT1) expression levels alters mouse mammary tumor cell growth in vitro and in vivo. PloS One. 6:e232052011. View Article : Google Scholar : PubMed/NCBI

42 

Sawayama H, Ishimoto T, Watanabe M, et al: High expression of glucose transporter 1 on primary lesions of esophageal squamous cell carcinoma is associated with hematogenous recurrence. Ann Surg Oncol. 21:1756–1762. 2014. View Article : Google Scholar : PubMed/NCBI

43 

Tohma T, Okazumi S, Makino H, et al: Overexpression of glucose transporter 1 in esophageal squamous cell carcinomas: a marker for poor prognosis. Dis Esophagus. 18:185–189. 2005. View Article : Google Scholar : PubMed/NCBI

44 

Kawamura T, Kusakabe T, Sugino T, et al: Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival. Cancer. 92:634–641. 2001. View Article : Google Scholar

45 

Jung JH, Im S, Jung ES and Kang CS: Clinicopathological implications of the expression of hypoxia-related proteins in gastric cancer. Int J Med Sci. 10:1217–1223. 2013. View Article : Google Scholar : PubMed/NCBI

46 

Haber RS, Rathan A, Weiser KR, et al: GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis. Cancer. 83:34–40. 1998. View Article : Google Scholar : PubMed/NCBI

47 

Korkeila E, Jaakkola PM, Syrjanen K, Pyrhonen S and Sundstrom J: Pronounced tumour regression after radiotherapy is associated with negative/weak glucose transporter-1 expression in rectal cancer. Anticancer Res. 31:311–315. 2011.PubMed/NCBI

48 

Kitamura K, Hatano E, Higashi T, et al: Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis. J Hepatol. 55:846–857. 2011. View Article : Google Scholar : PubMed/NCBI

49 

Legan M, Tevzic S, Tolar A, Luzar B and Marolt VF: Glucose transporter-1 (GLUT-1) immunoreactivity in benign, premalignant and malignant lesions of the gallbladder. Pathol Oncol Res. 17:61–66. 2011. View Article : Google Scholar : PubMed/NCBI

50 

Kim YW, Park YK, Yoon TY and Lee SM: Expression of the GLUT1 glucose transporter in gallbladder carcinomas. Hepatogastroenterology. 49:907–911. 2002.PubMed/NCBI

51 

Sattler UG and Mueller-Klieser W: The anti-oxidant capacity of tumour glycolysis. Int J Radiat Biol. 85:963–971. 2009. View Article : Google Scholar : PubMed/NCBI

52 

Hirschhaeuser F, Sattler UG and Mueller-Klieser W: Lactate: a metabolic key player in cancer. Cancer Res. 71:6921–6925. 2011. View Article : Google Scholar : PubMed/NCBI

53 

Brophy S, Sheehan KM, McNamara DA, Deasy J, Bouchier-Hayes DJ and Kay EW: GLUT-1 expression and response to chemoradiotherapy in rectal cancer. Int J Cancer. 125:2778–2782. 2009. View Article : Google Scholar : PubMed/NCBI

54 

Cao X, Fang L, Gibbs S, et al: Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes drug resistance in hypoxia. Cancer Chemother Pharmacol. 59:495–505. 2007. View Article : Google Scholar : PubMed/NCBI

55 

Wu CH, Ho YS, Tsai CY, et al: 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. 124:2210–2219. 2009. View Article : Google Scholar : PubMed/NCBI

56 

Liu Y, Cao Y, Zhang W, et al: 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. 11:1672–1682. 2012. View Article : Google Scholar : PubMed/NCBI

57 

Mathupala SP, Ko YH and Pedersen PL: Hexokinase-2 bound to mitochondria: cancer’s stygian link to the ‘Warburg Effect’ and a pivotal target for effective therapy. Semin Cancer Biol. 19:17–24. 2009.

58 

Kwee SA, Hernandez B, Chan O and Wong L: Choline kinase alpha and hexokinase-2 protein expression in hepatocellular carcinoma: association with survival. PloS One. 7:e465912012. View Article : Google Scholar : PubMed/NCBI

59 

Paudyal B, Paudyal P, Oriuchi N, Tsushima Y, Nakajima T and Endo K: Clinical implication of glucose transport and metabolism evaluated by 18F-FDG PET in hepatocellular carcinoma. Int J Oncol. 33:1047–1054. 2008.PubMed/NCBI

60 

Seo S, Hatano E, Higashi T, et al: Fluorine-18 fluorodeoxyglucose positron emission tomography predicts tumor differentiation, P-glycoprotein expression, and outcome after resection in hepatocellular carcinoma. Clin Cancer Res. 13:427–433. 2007. View Article : Google Scholar

61 

Ganapathy-Kanniappan S, Vali M, Kunjithapatham R, et al: 3-bromopyruvate: a new targeted antiglycolytic agent and a promise for cancer therapy. Curr Pharm Biotechnol. 11:510–517. 2010. View Article : Google Scholar : PubMed/NCBI

62 

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. 463:364–368. 2010. View Article : Google Scholar : PubMed/NCBI

63 

Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG and Krainer AR: The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci USA. 107:1894–1899. 2010. View Article : Google Scholar

64 

Christofk HR, Vander Heiden MG, Harris MH, et al: The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 452:230–233. 2008. View Article : Google Scholar : PubMed/NCBI

65 

Christofk HR, Vander Heiden MG, Wu N, Asara JM and Cantley LC: Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature. 452:181–186. 2008. View Article : Google Scholar : PubMed/NCBI

66 

Anastasiou D, Yu Y, Israelsen WJ, et al: Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol. 8:839–847. 2012. View Article : Google Scholar : PubMed/NCBI

67 

Yang W and Lu Z: Regulation and function of pyruvate kinase M2 in cancer. Cancer Lett. 339:153–158. 2013. View Article : Google Scholar : PubMed/NCBI

68 

Tamada M, Suematsu M and Saya H: Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells. Clin Cancer Res. 18:5554–5561. 2012. View Article : Google Scholar : PubMed/NCBI

69 

Kaplon J, Zheng L, Meissl K, et al: A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature. 498:109–112. 2013. View Article : Google Scholar : PubMed/NCBI

70 

Hur H, Xuan Y, Kim YB, et al: Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol. 42:44–54. 2013.PubMed/NCBI

71 

Lu CW, Lin SC, Chien CW, et al: Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. Am J Pathol. 179:1405–1414. 2011. View Article : Google Scholar : PubMed/NCBI

72 

Peifer C and Alessi DR: Small-molecule inhibitors of PDK1. Chem Med Chem. 3:1810–1838. 2008. View Article : Google Scholar : PubMed/NCBI

73 

Tong J, Xie G, He J, Li J, Pan F and Liang H: Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer. J Biomed Biotechnol. 2011:7405642011. View Article : Google Scholar : PubMed/NCBI

74 

Shen YC, Ou DL, Hsu C, et al: Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma. Br J Cancer. 108:72–81. 2013. View Article : Google Scholar

75 

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. 9:425–434. 2006. View Article : Google Scholar : PubMed/NCBI

76 

Goldman RD, Kaplan NO and Hall TC: Lactic dehydrogenase in human neoplastic tissues. Cancer Res. 24:389–399. 1964.PubMed/NCBI

77 

Fan J, Hitosugi T, Chung TW, et al: Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+) redox homeostasis in cancer cells. Mol Cell Biol. 31:4938–4950. 2011. View Article : Google Scholar : PubMed/NCBI

78 

Koukourakis MI, Giatromanolaki A, Sivridis E, Gatter KC and Harris AL: Lactate dehydrogenase 5 expression in operable colorectal cancer: strong association with survival and activated vascular endothelial growth factor pathway - a report of the Tumour Angiogenesis Research Group. J Clin Oncol. 24:4301–4308. 2006. View Article : Google Scholar

79 

Sheng SL, Liu JJ, Dai YH, Sun XG, Xiong XP and Huang G: Knockdown of lactate dehydrogenase A suppresses tumor growth and metastasis of human hepatocellular carcinoma. FEBS J. 279:3898–3910. 2012. View Article : Google Scholar

80 

Zhang Y, Zhang X, Wang X, et al: Inhibition of LDH-A by lentivirus-mediated small interfering RNA suppresses intestinaltype gastric cancer tumorigenicity through the downregulation of Oct4. Cancer Lett. 321:45–54. 2012. View Article : Google Scholar : PubMed/NCBI

81 

Le A, Cooper CR, Gouw AM, et al: Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci USA. 107:2037–2042. 2010. View Article : Google Scholar : PubMed/NCBI

82 

Miskimins WK, Ahn HJ, Kim JY, Ryu S, Jung YS and Choi JY: Synergistic anti-cancer effect of phenformin and oxamate. PloS One. 9:e855762014. View Article : Google Scholar : PubMed/NCBI

83 

Zhou M, Zhao Y, Ding Y, et al: Warburg effect in chemosensitivity: targeting lactate dehydrogenase-A re-sensitizes taxol-resistant cancer cells to taxol. Mol Cancer. 9:332010. View Article : Google Scholar : PubMed/NCBI

84 

Sumiyoshi Y, Kakeji Y, Egashira A, Mizokami K, Orita H and Maehara Y: Overexpression of hypoxia-inducible factor 1alpha and p53 is a marker for an unfavorable prognosis in gastric cancer. Clin Cancer Res. 12:5112–5117. 2006. View Article : Google Scholar : PubMed/NCBI

85 

Isobe T, Aoyagi K, Koufuji K, et al: Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1alpha) expression in gastric cancer. Int J Clin Oncol. 18:293–304. 2013. View Article : Google Scholar : PubMed/NCBI

86 

Theodoropoulos GE, Lazaris AC, Theodoropoulos VE, et al: Hypoxia, angiogenesis and apoptosis markers in locally advanced rectal cancer. Int J Colorectal Dis. 21:248–257. 2006. View Article : Google Scholar : PubMed/NCBI

87 

Dai CX, Gao Q, Qiu SJ, et al: Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery. BMC Cancer. 9:4182009. View Article : Google Scholar : PubMed/NCBI

88 

Liu L, Zhu XD, Wang WQ, et al: Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis. Clin Cancer Res. 16:2740–2750. 2010. View Article : Google Scholar : PubMed/NCBI

89 

Couvelard A, O’Toole D, Leek R, et al: Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas. Histopathology. 46:668–676. 2005. View Article : Google Scholar : PubMed/NCBI

90 

Shen YM, Arbman G, Olsson B and Sun XF: Overexpression of GLUT1 in colorectal cancer is independently associated with poor prognosis. Int J Biol Markers. 26:166–172. 2011. View Article : Google Scholar : PubMed/NCBI

91 

Pizzi S, Porzionato A, Pasquali C, et al: Glucose transporter-1 expression and prognostic significance in pancreatic carcinogenesis. Histol Histopathol. 24:175–185. 2009.PubMed/NCBI

92 

Rho M, Kim J, Jee CD, et al: Expression of type 2 hexokinase and mitochondria-related genes in gastric carcinoma tissues and cell lines. Anticancer Res. 27:251–258. 2007.PubMed/NCBI

93 

Qiu MZ, Han B, Luo HY, et al: Expressions of hypoxia-inducible factor-1alpha and hexokinase-II in gastric adenocarcinoma: the impact on prognosis and correlation to clinicopathologic features. Tumour Biol. 32:159–166. 2011. View Article : Google Scholar : PubMed/NCBI

94 

Gong L, Cui Z, Chen P, Han H, Peng J and Leng X: Reduced survival of patients with hepatocellular carcinoma expressing hexokinase II. Med Oncol. 29:909–914. 2012. View Article : Google Scholar

95 

Zhan C, Shi Y, Lu C and Wang Q: Pyruvate kinase M2 is highly correlated with the differentiation and the prognosis of esophageal squamous cell cancer. Dis Esophagus. 26:746–753. 2013.PubMed/NCBI

96 

Lim JY, Yoon SO, Seol SY, et al: Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer. World J Gastroenterol. 18:4037–4043. 2012. View Article : Google Scholar : PubMed/NCBI

97 

Li J, Yang Z, Zou Q, et al: PKM2 and ACVR 1C are prognostic markers for poor prognosis of gallbladder cancer. Clin Transl Oncol. 16:200–207. 2014. View Article : Google Scholar : PubMed/NCBI

98 

Kolev Y, Uetake H, Takagi Y and Sugihara K: Lactate dehydrogenase- 5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis. Ann Surg Oncol. 15:2336–2344. 2008. View Article : Google Scholar

99 

Yu SJ, Yoon JH, Yang JI, et al: Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition. J Bioenerg Biomembr. 44:101–115. 2012. View Article : Google Scholar

100 

Zhou Y, Tozzi F, Chen J, et al: Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res. 72:304–314. 2012. View Article : Google Scholar : PubMed/NCBI

101 

Vander Heiden MG, Christofk HR, Schuman E, et al: Identification of small molecule inhibitors of pyruvate kinase M2. Biochem Pharmacol. 79:1118–1124. 2010.PubMed/NCBI

102 

Feldman RI, Wu JM, Polokoff MA, et al: Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 280:19867–19874. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Sawayama H, Ishimoto T, Sugihara H, Miyanari N, Miyamoto Y, Baba Y, Yoshida N and Baba H: Clinical impact of the Warburg effect in gastrointestinal cancer (Review). Int J Oncol 45: 1345-1354, 2014.
APA
Sawayama, H., Ishimoto, T., Sugihara, H., Miyanari, N., Miyamoto, Y., Baba, Y. ... Baba, H. (2014). Clinical impact of the Warburg effect in gastrointestinal cancer (Review). International Journal of Oncology, 45, 1345-1354. https://doi.org/10.3892/ijo.2014.2563
MLA
Sawayama, H., Ishimoto, T., Sugihara, H., Miyanari, N., Miyamoto, Y., Baba, Y., Yoshida, N., Baba, H."Clinical impact of the Warburg effect in gastrointestinal cancer (Review)". International Journal of Oncology 45.4 (2014): 1345-1354.
Chicago
Sawayama, H., Ishimoto, T., Sugihara, H., Miyanari, N., Miyamoto, Y., Baba, Y., Yoshida, N., Baba, H."Clinical impact of the Warburg effect in gastrointestinal cancer (Review)". International Journal of Oncology 45, no. 4 (2014): 1345-1354. https://doi.org/10.3892/ijo.2014.2563
Copy and paste a formatted citation
x
Spandidos Publications style
Sawayama H, Ishimoto T, Sugihara H, Miyanari N, Miyamoto Y, Baba Y, Yoshida N and Baba H: Clinical impact of the Warburg effect in gastrointestinal cancer (Review). Int J Oncol 45: 1345-1354, 2014.
APA
Sawayama, H., Ishimoto, T., Sugihara, H., Miyanari, N., Miyamoto, Y., Baba, Y. ... Baba, H. (2014). Clinical impact of the Warburg effect in gastrointestinal cancer (Review). International Journal of Oncology, 45, 1345-1354. https://doi.org/10.3892/ijo.2014.2563
MLA
Sawayama, H., Ishimoto, T., Sugihara, H., Miyanari, N., Miyamoto, Y., Baba, Y., Yoshida, N., Baba, H."Clinical impact of the Warburg effect in gastrointestinal cancer (Review)". International Journal of Oncology 45.4 (2014): 1345-1354.
Chicago
Sawayama, H., Ishimoto, T., Sugihara, H., Miyanari, N., Miyamoto, Y., Baba, Y., Yoshida, N., Baba, H."Clinical impact of the Warburg effect in gastrointestinal cancer (Review)". International Journal of Oncology 45, no. 4 (2014): 1345-1354. https://doi.org/10.3892/ijo.2014.2563
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