ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma

Oncotarget. 2016 Aug 9;7(32):51829-51839. doi: 10.18632/oncotarget.10386.

Abstract

Renal cell carcinoma (RCC) is the major cause of kidney malignancy-related deaths. Rho GTPases are key regulators in cancer cell metastasis. ARHGAP24, a Rac-specific member of the Rho GTPase-activating protein family, acts as a functional target of cancer cell migration and invasion. In the present study, we identified ARHGAP24 expression is downregulated in renal cancer tissues and is highly correlated with long-term survival in RCC patients. Therefore, we investigated the biological functions of ARHGAP24 in renal cancer cells. Ectopic expression of ARHGAP24 resulted in inhibited cell proliferation and arrested cell cycle in two renal cancer cell lines (786-0 and Caki-2); the results were confirmed by ARHGAP24 knocking down. In addition, ARHGAP24 significantly reduced the cell invasion ability and induced apoptosis in renal cancer cells. In addition, overexpressing ARHGAP24 impaired tumor formation in vivo. In summary, our results illustrated that ARHGAP24 plays a unique role in RCC progression as a tumor repressor.

Keywords: ARHGAP24; apoptosis; cell cycle; proliferation; renal cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis / genetics*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Cycle / genetics*
  • Cell Division / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • GTPase-Activating Proteins / physiology*
  • Genes, Tumor Suppressor*
  • HEK293 Cells
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness

Substances

  • ARHGAP24 protein, human
  • GTPase-Activating Proteins