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LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma

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Tumor Biology

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors in the world, and the development of new therapeutic targets is needed. Recent studies have shown that aerobic glycolysis, also known as the Warburg effect, mediated the anti-apoptotic effects in cancer cells. Lactate dehydrogenase A (LDHA) which executed the final step of aerobic lactate production has been reported to be involved in the tumor progression. However, the function of LDHA in ESCC has not been investigated. In this study, it was found that LDHA was up-regulated in ESCC clinical samples. Knockdown of the expression of LDHA inhibited cell growth and cell migration in vitro as well as tumorigenesis in vivo. With regard to the molecular mechanism, silencing the expression of LDHA was related to decreased AKT activation and cyclin D1 expression and increased cleavage of PARP and caspase 8. Taken together, our findings suggest that LDHA plays an important role in the progression of ESCC by modulating cell growth, and LDHA might be a potential therapeutic target in ESCC.

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Reference

  1. Deng YZ, Chen PP, Wang Y, Yin D, Koeffler HP, Li B, et al. Connective tissue growth factor is overexpressed in esophageal squamous cell carcinoma and promotes tumorigenicity through beta-catenin-T-cell factor/Lef signaling. J Biol Chem. 2007;282(50):36571–81.

    Article  PubMed  CAS  Google Scholar 

  2. Zhou ZQ, Cao WH, Xie JJ, et al. Expression and prognostic significance of THBS1, Cyr61 and CTGF in esophageal squamous cell carcinoma. BMC Cancer. 2009;9:291.

    Article  PubMed  Google Scholar 

  3. Warburg O. On the origin of cancer cells. Science. 1956;123:309–14.

    Article  PubMed  CAS  Google Scholar 

  4. Lewis BC, Shim H, Li Q, et al. Identification of putative c-Myc-responsive genes: characterization of rcl, a novel growth-related gene. Mol Cell Biol. 1997;17:967–78.

    Google Scholar 

  5. Shim H, Dolde C, Lewis BC, et al. C-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci USA. 1997;94:6658–63.

    Article  PubMed  CAS  Google Scholar 

  6. Cai Z, Zhao JS, Li JJ, et al. A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism. Mol Cell Proteomics. 2010;9(12):2617–28.

    Article  PubMed  CAS  Google Scholar 

  7. Huang L, Zheng M, Zhou QM, et al. Identification of a gene-expression signature for predicting lymph node metastasis in patients with early stage cervical carcinoma. Cancer. 2011;117(15):3363–73.

    Article  PubMed  CAS  Google Scholar 

  8. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004;4(11):891–9.

    Article  PubMed  CAS  Google Scholar 

  9. Gillies RJ, Robey I, Gatenby RA. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med. 2008;49:24S–42.

    Article  PubMed  CAS  Google Scholar 

  10. Martínez-Zaguilán R, Seftor EA, Seftor RE, et al. Acidic pH enhances the invasive behavior of human melanoma cells. Clin Exp Metastasis. 1996;14:176–86.

    Article  PubMed  Google Scholar 

  11. Schlappack OK, Zimmermann A, Hill PR. Glucose starvation and acidosis: effect on experimental metastatic potential, DNA content and MTX resistance of murine tumour cells. Br J Cancer. 1991;64:663–70.

    Article  PubMed  CAS  Google Scholar 

  12. Firth J, Ebert B, Pugh C, et al. Oxygen-regulated control elements in the phosphoglycerate kinase I and lactate dehydrogenase A genes: similarities with the erythropoietin 3′enhancer. Proc Natl Acad Sci USA. 1994;91:6496–500.

    Article  PubMed  CAS  Google Scholar 

  13. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006;6:425–34.

    Article  Google Scholar 

  14. Dang CV, Semenza GL. Oncogenic alterations of metabolism. Trends Biochem Sci. 1999;24:68–72.

    Article  PubMed  CAS  Google Scholar 

  15. Maher JC, Krishan A, Lampidis T. Greater cell cycle inhibition and cytotoxicity induced by 2-deoxy-d-glucose in tumor cells treated under hypoxic vs aerobic condition. Cancer Chemother Pharmacol. 2004;53:116–22.

    Article  PubMed  CAS  Google Scholar 

  16. Maschek G, Savaraj N, Priebe W, et al. 2-Deoxy-d-glucose increases the efficacy of Adriamycin and paclitaxel in human osteosarcoma and nonsmall cell lung cancers in vivo. Cancer Res. 2004;64:31–4.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Tiejun Zhao or Heng Zhao.

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Feng Yao and Tiejun Zhao contributed equally to this work.

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Yao, F., Zhao, T., Zhong, C. et al. LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma. Tumor Biol. 34, 25–31 (2013). https://doi.org/10.1007/s13277-012-0506-0

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  • DOI: https://doi.org/10.1007/s13277-012-0506-0

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