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

Acta Pharmacol Sin. 2012 Jun;33(6):817-22. doi: 10.1038/aps.2012.30. Epub 2012 Apr 30.


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 Ca(2+)-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 CDH1-siRNA for 24-96 h significantly suppressed the growth and proliferation of SKOV-3 cells. E-cadherin-mediated 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 μmol/L), but not by the PI3K inhibitor wortmannin (1 μmol/L) or PKA inhibitor H89 (10 μmol/L).

Conclusion: E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • MAP Kinase Signaling System*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • RNA Interference


  • Cadherins