Wnt5a promotes vasculogenic mimicry and epithelial-mesenchymal transition via protein kinase Cα in epithelial ovarian cancer

Oncol Rep. 2014 Aug;32(2):771-9. doi: 10.3892/or.2014.3229. Epub 2014 Jun 4.


Epithelial ovarian cancer is one of the most common causes of cancer-related death in women. The majority of epithelial ovarian cancer patients present with metastasis at the time of initial diagnosis. Studies have demonstrated that vasculogenic mimicry (VM) is highly correlated with metastasis and invasiveness, and epithelial-mesenchymal transition (EMT) is pivotal in VM formation. Wnt5a, a member of the Wnt protein family, can activate the non-canonical Wnt signaling pathway mediating cancer initiation and progression. Thus, the present study aimed to investigate the relationship between Wnt5a and VM and its mechanism in epithelial ovarian cancer. The present results showed that Wnt5a staining was significantly correlated with metastasis in epithelial ovarian cancer. The correlation between the expression of Wnt5a and VM or protein kinase Cα (PKCα) indicated that Wnt5a was associated with VM and may be linked to the PKC pathway. In vitro experiments revealed that Wnt5a enhanced the vasculogenic capacity, motility and invasiveness of ovarian cancer cells; however, the PKCα inhibitor blocked these effects. Western blot analysis showed that changes in Wnt5a expression coincided with changes in PKC expression and that PI3K and Snail expression increased along with Wnt5a upregulation. However, no change was observed in β-catenin levels, indicating that Wnt5a may mediate EMT and VM in ovarian cancer cells via the PKCα pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Metastasis / pathology
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology*
  • Neovascularization, Pathologic / metabolism*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Protein Kinase C-alpha / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction
  • Wnt Proteins / metabolism*
  • Wnt-5a Protein
  • Young Adult


  • Proto-Oncogene Proteins
  • WNT5A protein, human
  • Wnt Proteins
  • Wnt-5a Protein
  • PRKCA protein, human
  • Protein Kinase C-alpha