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

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 aggressive...

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Published inThe Journal of cell biology Vol. 212; no. 2; pp. 199 - 217
Main Authors Plutoni, Cédric, Bazellieres, Elsa, Le Borgne-Rochet, Maïlys, Comunale, Franck, Brugues, Agusti, Séveno, Martial, Planchon, Damien, Thuault, Sylvie, Morin, Nathalie, Bodin, Stéphane, Trepat, Xavier, Gauthier-Rouvière, Cécile
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 18.01.2016
The Rockefeller University Press
Subjects
Animals
Anisotropy
Biochemistry, Molecular Biology
Biomechanical Phenomena
Cadherins - metabolism
Cancer
cdc42 GTP-Binding Protein - metabolism
Cell Movement
Cell Polarity
Cells, Cultured
Cellular Biology
Life Sciences
Mice
Morphogenesis
Myoblasts - cytology
Myoblasts - metabolism
Proteins
Rho Guanine Nucleotide Exchange Factors - metabolism
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Summary: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/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-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 β-PIX-mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.
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ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201505105