The role of RhoC in epithelial-to-mesenchymal transition of ovarian carcinoma cells

BMC Cancer. 2014 Jul 1;14:477. doi: 10.1186/1471-2407-14-477.

Abstract

Background: RhoC is a small G protein/GTPase and involved in tumor mobility, invasion and metastasis. Previously, up-regulated RhoC expression is found to play an important role in ovarian carcinogenesis and subsequent progression by modulating proliferation, apoptosis, migration and invasion.

Methods: We transfected RhoC-expressing plasmid and RhoC siRNA into CAOV3 and OVCAR3 cells respectively. These cells and transfectants were exposed to vascular epithelial growth factor (VEGF), transforming growth factor (TGF)-β1 or their receptor inhibitors with the phenotypes and their related-molecules examined.

Results: TGF-β1R or VEGFR inhibitor suppressed the proliferation, migration, invasion and lamellipodia formation, the expression of N-cadherin, α-SMA, snail and Notch1 mRNA or protein, and enhanced E-cadherin mRNA and protein expression in CAOV3 and its RhoC-overexpressing transfectants, whereas both growth factors had the opposite effects in OVCAR3 cells and their RhoC-hypoexpressing transfectants. Ectopic RhoC expression enhanced migration, invasion, lamellipodia formation and the alteration in epithelial to mesenchymal transition (EMT) markers of CAOV3 cells regardless of the treatment of VEGFR or TGF-β1R inhibitor, whereas RhoC knockdown resulted in the converse in OVCAR3 cells even with the exposure to VEGF or TGF-β1.

Conclusion: RhoC expression might be involved in EMT of ovarian epithelial carcinoma cells, stimulated by TGF-β1 and VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism
  • Carcinoma / genetics*
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression
  • Humans
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • rho GTP-Binding Proteins / genetics*
  • rho GTP-Binding Proteins / metabolism
  • rhoC GTP-Binding Protein

Substances

  • Cadherins
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoC GTP-Binding Protein