P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces.
J Cell Biol
; 212(2): 199-217, 2016 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-26783302
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/ß-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through ß-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 ß-PIX-mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caderinas
/
Movimento Celular
/
Proteína cdc42 de Ligação ao GTP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2016
Tipo de documento:
Article