VE-cadherin cleavage by ovarian cancer microparticles induces β-catenin phosphorylation in endothelial cells

Hamda Al Thawadi, Nadine Abu-Kaoud, Haleema Al Farsi, Jessica Hoarau, Shahin Rafii, Arash Rafii Tabrizi, Jennifer Pasquier

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Microparticles (MPs) are increasingly recognized as important mediators of cell-cell communication in tumour growth and metastasis by facilitating angiogenesis-related processes. While the effects of the MPs on recipient cells are usually well described in the literature, the leading process remains unclear. Here we isolated MPs from ovarian cancer cells and investigated their effect on endothelial cells. First, we demonstrated that ovarian cancer MPs trigger β-catenin activation in endothelial cells, inducing the upregulation of Wnt/β-catenin target genes and an increase of angiogenic properties. We showed that this MPs mediated activation of β-catenin in ECs was Wnt/Frizzled independent; but dependent on VE-cadherin localization disruption, αVβ3 integrin activation and MMP activity. Finally, we revealed that Rac1 and AKT were responsible for β-catenin phosphorylation and translocation to the nucleus. Overall, our results indicate that MPs released from cancer cells could play a major role in neo-angiogenesis through activation of beta catenin pathway in endothelial cells.

Original languageEnglish
Pages (from-to)5289-5305
Number of pages17
JournalOncotarget
Volume7
Issue number5
DOIs
Publication statusPublished - 2016

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Keywords

  • Angiogenesis
  • Microparticles
  • Ovarian cancer
  • Tumor microenvironment
  • β-catenin

ASJC Scopus subject areas

  • Oncology

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