The role of RhoC in epithelial-to-mesenchymal transition of ovarian carcinoma cells
1 Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University, 121001 Jinzhou, China
2 Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, The First Affiliated Hospital of Liaoning Medical University, 121001 Jinzhou, China
3 Department of Gynecology, The First Affiliated Hospital of China Medical University, 110001 Shenyang, China
4 Department of Oncological Medicine, The First Affiliated Hospital of China Medical University, 110001 Shenyang, China
5 Department of Physiology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 110016 Shenyang, China
6 Clinical Research Institute, Kanagawa Cancer Center, 241-0815 Yokohama, Japan
BMC Cancer 2014, 14:477 doi:10.1186/1471-2407-14-477Published: 1 July 2014
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.
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.
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.
RhoC expression might be involved in EMT of ovarian epithelial carcinoma cells, stimulated by TGF-β1 and VEGF.