LDHA promotes tumor metastasis by facilitating epithelial‑mesenchymal transition in renal cell carcinoma

  • Authors:
    • Juping Zhao
    • Xin Huang
    • Zhaoping Xu
    • Jun Dai
    • Hongchao He
    • Yu Zhu
    • Haofei Wang
  • View Affiliations

  • Published online on: September 27, 2017     https://doi.org/10.3892/mmr.2017.7637
  • Pages:8335-8344
0

Abstract

Previous studies have indicated that high expression of lactate dehydrogenase A (LDHA) exists in many human cancers. Recently, several reports showed that silencing or inhibition of LDHA could suppress metastasis of human cancer including renal cell carcinoma (RCC). However, the mechanism remains unknown. The role of LDHA in RCC migration and invasion was investigated using immunohistochemistry, western blotting, Transwell and scratch assays, and in vivo experiment. The influence of LDHA on the Warburg effect was also investigated by LDHA activity and lactate production assay. LDHA was overexpressed in RCC tissues and predicted a worse survival following renal resection. Correlation analysis demonstrated that LDHA was negatively correlated with E‑cadherin and positively with N‑cadherin. Experimentally, both in vivo and in vitro experiments found downregulation of LDHA suppressed RCC cells migration and invasion by inhibiting EMT. In addition, results indicated LDHA could promote the Warburg effect. Further research presented that the LDHA inhibitor, oxamate, suppressed tumor metastasis by inhibiting LDHA activity and EMT. These results demonstrated that LDHA mediates tumor metastasis by promoting EMT in RCC, suggesting that LDHA could be a promising therapeutic target for RCC therapy.

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December 2017
Volume 16 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Zhao, J., Huang, X., Xu, Z., Dai, J., He, H., Zhu, Y., & Wang, H. (2017). LDHA promotes tumor metastasis by facilitating epithelial‑mesenchymal transition in renal cell carcinoma. Molecular Medicine Reports, 16, 8335-8344. https://doi.org/10.3892/mmr.2017.7637
MLA
Zhao, J., Huang, X., Xu, Z., Dai, J., He, H., Zhu, Y., Wang, H."LDHA promotes tumor metastasis by facilitating epithelial‑mesenchymal transition in renal cell carcinoma". Molecular Medicine Reports 16.6 (2017): 8335-8344.
Chicago
Zhao, J., Huang, X., Xu, Z., Dai, J., He, H., Zhu, Y., Wang, H."LDHA promotes tumor metastasis by facilitating epithelial‑mesenchymal transition in renal cell carcinoma". Molecular Medicine Reports 16, no. 6 (2017): 8335-8344. https://doi.org/10.3892/mmr.2017.7637