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
-
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 - Published online on: July 25, 2014 https://doi.org/10.3892/ijo.2014.2563
- Pages: 1345-1354
This article is mentioned in:
Abstract
Warburg O: On respiratory impairment in cancer cells. Science. 124:269–270. 1956.PubMed/NCBI | |
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 | |
Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI | |
Plathow C and Weber WA: Tumor cell metabolism imaging. J Nucl Med. 49(Suppl 2): S43–S63. 2008. View Article : Google Scholar | |
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 | |
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 | |
Vousden KH and Ryan KM: p53 and metabolism. Nat Rev Cancer. 9:691–700. 2009. View Article : Google Scholar | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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. | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
Amente S, Lania L and Majello B: Epigenetic reprogramming of Myc target genes. Am J Cancer Res. 1:413–418. 2011.PubMed/NCBI | |
de Souza CR, Leal MF, Calcagno DQ, et al: MYC deregulation in gastric cancer and its clinicopathological implications. PloS One. 8:e644202013.PubMed/NCBI | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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. | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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. | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
Peifer C and Alessi DR: Small-molecule inhibitors of PDK1. Chem Med Chem. 3:1810–1838. 2008. View Article : Google Scholar : PubMed/NCBI | |
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 | |
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 | |
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 | |
Goldman RD, Kaplan NO and Hall TC: Lactic dehydrogenase in human neoplastic tissues. Cancer Res. 24:389–399. 1964.PubMed/NCBI | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 |