| First Author | Plutoni C | Year | 2016 |
| Journal | J Cell Biol | Volume | 212 |
| Issue | 2 | Pages | 199-217 |
| PubMed ID | 26783302 | Mgi Jnum | J:230823 |
| Mgi Id | MGI:5766103 | Doi | 10.1083/jcb.201505105 |
| Citation | Plutoni C, et al. (2016) P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces. J Cell Biol 212(2):199-217 |
| abstractText | 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/beta-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through beta-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 beta-PIX-mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM. |
