title: VE-cadherin cleavage by ovarian cancer microparticles induces β-catenin phosphorylation in endothelial cells.
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.
authors.affiliation: Qatar Research Leadership Program, Qatar Foundation, Doha, Qatar.|Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
authors.forename: Hamda
authors.initials: H
authors.lastname: Al Thawadi
authors.affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
authors.forename: Nadine
authors.initials: N
authors.lastname: Abu-Kaoud
authors.affiliation: Qatar Research Leadership Program, Qatar Foundation, Doha, Qatar.|Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
authors.forename: Haleema
authors.initials: H
authors.lastname: Al Farsi
authors.affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hoarau-Véchot
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, NY, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.|Department of Genetic Medicine, Weill Cornell Medical College, NY, USA.
authors.forename: Arash
authors.initials: A
authors.lastname: Rafii
authors.affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.|Department of Genetic Medicine, Weill Cornell Medical College, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pasquier
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction; D059016:Tumor Microenvironment; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051176:beta Catenin
keywords: angiogenesis; microparticles; ovarian cancer; tumor microenvironment; β-catenin