E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway

Aim： E-cadherin is unusually highly expressed in most ovarian cancers. This study was designed to investigate the roles of E-cadherin in the carcinogenesis and progression of ovarian cancers. Methods： Human ovarian adenocarcinoma cell line SKOV-3 was examined. E-cadherin gene CDH1 in SKOV-3 cells was knocked down via RNA interference （RNAi）, and the resultant variation of biological behavior was observed using CCK-8 and colony formation experiment. E-cadherin-mediated Ca2＋-dependent cell-cell adhesion was used to study the mechanisms underlying the effects of E-cadherin on the proliferation and survival of SKOV-3 cells. The expression levels of E-cadherin, extracellular signal-related kinase （ERK）, phosphorylated ERK （P-ERK） were measured using Western blot assays. Results： Transfection with CDHI-siRNA for 24-96 h significantly suppressed the growth and proliferation of SKOV-3 cells. E-cadherinmediated calcium-dependent cell-cell adhesion of SKOV-3 cells resulted in a rapid increase of P-ERK, but did not modify the expression of ERK protein. The phosphorylation of ERK in the cells was blocked by pretreatment with the MEK1 specific inhibitor PD98059 （50 pmol/L）, but not by the PI3K inhibitor wortmannin （1 pmol/L） or PKA inhibitor H89 （10 pmol/L）. Conclusion： E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.