P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces.

ABSTRACT: Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell-cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/?-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through ?-PIX, which is specifically recruited at cell-cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through ?-PIX-mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.

SUBMITTER: Plutoni C 

PROVIDER: S-EPMC4738379 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature