Rap2a serves as a potential prognostic indicator of renal cell carcinoma and promotes its migration and invasion through up-regulating p-Akt

Sci Rep. 2017 Jul 26;7(1):6623. doi: 10.1038/s41598-017-06162-7.

Abstract

Rap2a, a member of the small GTPase superfamily, belongs to Ras superfamily, and its function in cancer progression is still poorly understood. Our previous study indicated that the ectopic expression of Rap2a enhanced the migration and invasion ability of lung cancer cells. However, its expression and molecular mechanism on renal cell carcinoma (RCC) have not been characterized. This study explored the clinical significance and biological function of Rap2a in human RCC. The clinical relevance of Rap2a in RCC was evaluated by immunohistochemical staining using tissue microarray. Our data showed that Rap2a expression was dramatically increased in RCC tissues compared with normal renal tissues. The ectopic expression of Rap2a enhanced the migration and invasive ability of cancer cells. In contrast, downregulation of Rap2a inhibited cell invasion. Rap2a had no effect on the proliferation of RCC cell lines. Meanwhile, Rap2a can regulate the phosphorylation level of Akt in vitro. In vivo studies also showed that Rap2a positively regulated metastasis of renal cancer cells and the expression of p-Akt. These findings indicate that Rap2a promotes RCC metastasis and may serve as a candidate RCC prognostic marker and a potential therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Tissue Array Analysis
  • rap GTP-Binding Proteins / analysis*

Substances

  • Biomarkers, Tumor
  • RAP2A protein, human
  • rap GTP-Binding Proteins