RhoA and Rac mediate endothelial cell polarization and detachment induced by T‐cadherin

Abstract
SPECIFIC AIMST-cadherin (T-cad) is an atypical GPI-anchored member of the cadherin superfamily, which does not mediate intercellular adhesion and has been proposed to function as a signaling receptor regulating directed cell migration. During embryogenesis T-cad acts as a negative guidance cue for extending neurites. In vascular tissue T-cad is up-regulated under conditions (atherosclerosis, restenosis, and tumor angiogenesis) associated with abnormal cell migration, growth, and phenotypic modulation. In cultured human umbilical vein endothelial cells (HUVEC), homophilic T-cad ligation induces cell polarization to a migratory phenotype, decreases cell adhesion to the substratum, and facilitates cell motility. Signaling mechanisms mediating T-cad effects have never been investigated. The present study aimed to elucidate a potential role for RhoA/Rho-kinase (ROCK) and Rac pathways in T-cad-induced endothelial cell polarization.PRINCIPAL FINDINGS1. RhoA activation is necessary but not sufficient for T-cad-in...
Funding Information
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31-58826.99, 31-105406.1)
  • Novartis Stiftung für Medizinisch-Biologische Forschung