p120-catenin differentially regulates cell migration by Rho-dependent intracellular and secreted signals

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 or 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 increase of actin stress fibers, reduction in integrin turnover, and an increase in focal adhesions robustness. 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. Total RNA from the backskin of p120L/L -K5Cre+/+ or p120Δ/Δ -K5Cre+/T mouse embryos (E18.5) was isolated. The RNA quality (between 6.7 to 8.8) was confirmed using an Agilent 2100 Bioanalyzer. The amount of nucleic acid labeled was 1 µg and amplification was performed using the Commercial Two-Color Microarray-Based Gene Expression Analysis (Quick Amp Labeling) kit following the manufacturer’s instructions. (Agilent manual G4140-90050 Ver. 5.7 March 2008.) The microarray used was Mouse WMG 4X44K (Agilent microarray design ID 014868, P/N G4122F). The amount of each labeled nucleic acid extracted was 825 ng in a final volume of 100 µl. The hybridization was performed at 65 ºC for 17 h and the scan was performed on a G2565C DNA microarray scanner (Agilent). Images were quantified using the Agilent Feature Extraction Software (ver. 10.1.1).