title: p120-catenin differentially regulates cell migration by Rho-dependent intracellular and secreted signals.
abstract: The adherens junction protein p120-catenin is implicated in the regulation of cadherin stability, cell migration and inflammatory responses in mammalian epithelial tissues. How these events are coordinated to promote wound repair is not understood. We show that p120 catenin regulates the intrinsic migratory properties of primary mouse keratinocytes, but also influences the migratory behavior of neighboring cells by secreted signals. These events are rooted in the ability of p120-catenin to regulate RhoA GTPase activity, which leads to a two-tiered control of cell migration. One restrains cell motility via an increase in actin stress fibers, reduction in integrin turnover and an increase in the robustness of focal adhesions. The other is coupled to the secretion of inflammatory cytokines including interleukin-24, which causally enhances randomized cell movements. Taken together, our results indicate that p120-RhoA-GTPase-mediated signaling can differentially regulate the migratory behavior of epidermal cells, which has potential implications for chronic wound responses and cancer.
authors.affiliation: Epithelial Cell Biology Group BBVA Foundation-Spanish National Cancer Research Centre (CNIO) Cancer Cell Biology Programme, CNIO, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Epifano
authors.forename: Diego
authors.initials: D
authors.lastname: Megias
authors.forename: Mirna
authors.initials: M
authors.lastname: Perez-Moreno
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D022001:Focal Adhesions / Q000378:metabolism; D016023:Integrins / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology; D051379:Mice; D015398:Signal Transduction; D014945:Wound Healing / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; D000099180:Interleukin-24
chemical_list: D051177:Catenins; D016023:Integrins; D007378:Interleukins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; D000099180:Interleukin-24; C526380:RhoA protein, mouse; C000722349:Ctnnd1 protein, mouse