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Lactate dehydrogenase A is overexpressed in pancreatic cancer and promotes the growth of pancreatic cancer cells - Tumor Biology

  • ️Lou, Wenhui
  • ️Wed Feb 13 2013

Abstract

The prognosis for pancreatic cancer is very poor, and developing new therapeutic strategies for this cancer is needed. Recently, the Warburg effect (aerobic glycolysis) has attracted much attention for its function in the tumorigenesis. Lactate dehydrogenase A (LDHA) executes the final step of aerobic glycolysis and has been reported to be involved in the tumor progression. However, the function of LDHA in pancreatic cancer has not been studied. Here, we found that the expression of LDHA was elevated in the clinical pancreatic cancer samples. Forced expression of LDHA promoted the growth of pancreatic cancer cells, while knocking down the expression of LDHA inhibited cell growth dramatically. Moreover, silencing the expression of LDHA inhibited the tumorigenicity of pancreatic cancer cells in vivo. Mechanistically, knocking down the expression of LDHA activated apoptosis pathway. Taken together, our study revealed the oncogenic role of LDHA in pancreatic cancer and suggested that LDHA might be a potential therapeutic target.

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References

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2009;59:225–49.

    Article  PubMed  Google Scholar 

  2. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2008;58:71–96.

    Article  PubMed  Google Scholar 

  3. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas—616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567–79.

    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. Yao F, Zhao T, Zhong C, et al. LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma. Tumor Biol. 2012;34:25–31.

    Article  Google Scholar 

  7. Cai Z, Zhao JS, Li JJ, et al. A combined proteomic and metabolomic profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism. Mol Cell Proteomics. 2010;9:2617–28.

    Article  PubMed  CAS  Google Scholar 

  8. Warshaw AL, Fernandez-del CC. Pancreatic carcinoma. N Engl J Med. 1992;316:455–65.

    Article  Google Scholar 

  9. Hidalgo M. Pancreatic cancer. N Engl J Med. 1992;362:1605–17.

    Article  Google Scholar 

  10. Hruban RH et al. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6:2969–72.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. 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 

  14. 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 

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

    Article  PubMed  CAS  Google Scholar 

  16. Sheng SL, Liu JJ, Dai YH, et al. Knockdown of lactate dehydrogenase A suppresses tumor growth and metastasis of human hepatocellular carcinoma. FEBS J. 2012;279:3898–910.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Shanghai Science and Technology Fund JC1402200 and the Research Special Fund for Public Welfare Industry of Health 201202007.

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Authors and Affiliations

  1. Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan University, 180th Feng Lin Road, Shanghai, 200031, China

    Yefei Rong, Wenchuan Wu, Xiaoling Ni, Tiantao Kuang, Dayong Jin, Dansong Wang & Wenhui Lou

Authors

  1. Yefei Rong

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  2. Wenchuan Wu

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  3. Xiaoling Ni

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  4. Tiantao Kuang

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  5. Dayong Jin

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  6. Dansong Wang

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  7. Wenhui Lou

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Corresponding authors

Correspondence to Dansong Wang or Wenhui Lou.

Additional information

Yefei Rong and Wenchuan Wu contributed equally to this work.

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Rong, Y., Wu, W., Ni, X. et al. Lactate dehydrogenase A is overexpressed in pancreatic cancer and promotes the growth of pancreatic cancer cells. Tumor Biol. 34, 1523–1530 (2013). https://doi.org/10.1007/s13277-013-0679-1

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  • Received: 26 November 2012

  • Accepted: 28 January 2013

  • Published: 13 February 2013

  • Issue Date: June 2013

  • DOI: https://doi.org/10.1007/s13277-013-0679-1

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