VE-cadherin cleavage by ovarian cancer microparticles induces β-catenin phosphorylation in endothelial cells. Academic Article uri icon

Overview

MeSH

  • Female
  • Humans
  • Phosphorylation
  • Signal Transduction
  • Tumor Microenvironment

MeSH Major

  • Cadherins
  • Endothelial Cells
  • Ovarian Neoplasms
  • beta Catenin

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.

publication date

  • February 2, 2016

has subject area

  • Cadherins
  • Endothelial Cells
  • Female
  • Humans
  • Ovarian Neoplasms
  • Phosphorylation
  • Signal Transduction
  • Tumor Microenvironment
  • beta Catenin

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4868686

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.6677

PubMed ID

  • 26700621

Additional Document Info

start page

  • 5289

end page

  • 5305

volume

  • 7

number

  • 5