Abstract 1289: Cooperation between beta-catenin, Snail, Slug, and Twist is required for maximum repression of the human vascular endothelial-cadherin promoter

Abstract

Abstract Vascular endothelial (VE)-cadherin is a key protein in the adherens junctions. This protein forms homophilic intercellular interactions and is required for the integrity of the endothelial monolayer, endothelial permeability, and control of cell growth. We have previously demonstrated that exposure of endothelial cells to breast cancer cell-conditioned media results in upregulation of Twist, Slug, and Snail expression, which in turn downregulate the activity of the human VE-cadherin promoter through at least two E-box motifs. Since these repressors have been linked to the β-catenin signaling pathway, we chose to determine whether β-catenin could regulate the activity of the human VE-cadherin promoter. Herein, we demonstrate that β-catenin represses the VE-cadherin promoter either alone or in coordination with the repressors Twist, Slug, and Snail. Electrophoretic mobility shift assays showed that the VE-cadherin promoter contains four β-catenin/LEF-1 binding motifs (designated Site-1-4) that appear to be involved in this regulatory process. In addition, we identified TGFβ as one of the factors released by breast cancer cells that could be involved in the regulation of the VE-cadherin gene when HDMEC are exposed to breast cancer cell conditioned medium. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1289. doi:1538-7445.AM2012-1289