TY - JOUR

T1 - p120-catenin differentially regulates cell migration by Rho-dependent intracellular and secreted signals

AU - Epifano, Carolina

AU - Megias, Diego

AU - Perez-Moreno, Mirna

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Actin Cytoskeleton

KW - Animals

KW - Catenins

KW - Cell Adhesion

KW - Cell Movement

KW - Cells, Cultured

KW - Focal Adhesions

KW - Integrins

KW - Interleukins

KW - Keratinocytes

KW - Mice

KW - Signal Transduction

KW - Wound Healing

KW - rho GTP-Binding Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/embr.201337868

DO - 10.1002/embr.201337868

M3 - Journal article

C2 - 24639556

VL - 15

SP - 592

EP - 600

JO - E M B O Reports

JF - E M B O Reports

SN - 1469-221X

IS - 5

ER -