WAVE1 gene silencing via RNA interference reduces ovarian cancer cell invasion, migration and proliferation

Gynecol Oncol. 2013 Aug;130(2):354-61. doi: 10.1016/j.ygyno.2013.05.005. Epub 2013 May 13.

Abstract

Objective: Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) has been implicated in cancer cell migration and invasion. We have previously shown that the overexpression of WAVE1 in epithelial ovarian cancer (EOC) tissues is associated with a poor prognosis. However, the mechanism of WAVE1 regulating the malignant behaviors in EOC remains unclear.

Methods: In the present study, we knocked down WAVE1 expression in SKOV3 and OVCAR-3 cells through RNA interference to detect the cell biology and molecular biology changes. Moreover, western-blot was used to investigate the underlying mechanism of WAVE1 regulating the proliferative and invasive malignant behaviors in ovarian cancer cells.

Results: The down-regulation of WAVE1 had a significant effect on cell morphological changes. WAVE1 silencing decreased cell migration, cell invasion, cell adhesion, colony formation and cell proliferation in vitro. In addition, we found that down-regulation of WAVE1 inhibited malignant behaviors in vivo. Furthermore, our study also indicated that the PI3K/AKT and p38MAPK signaling pathways might contribute to WAVE1 promotion of ovarian cancer cell proliferation, migration, and invasion.

Conclusions: WAVE1 might promote the proliferative and invasive malignant behaviors through the activation of the PI3K/AKT and p38MAPK signaling pathways in EOC.

Keywords: Invasion; Ovarian cancer; Proliferation; RNA interference; WAVE1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Silencing
  • Humans
  • Mice
  • Neoplasm Invasiveness
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Proto-Oncogene Proteins c-akt / physiology
  • RNA Interference
  • Wiskott-Aldrich Syndrome Protein Family / genetics
  • Wiskott-Aldrich Syndrome Protein Family / physiology*
  • p38 Mitogen-Activated Protein Kinases / physiology

Substances

  • WASF1 protein, human
  • Wiskott-Aldrich Syndrome Protein Family
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases