期刊
JOURNAL OF CELL BIOLOGY
卷 212, 期 2, 页码 199-217出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201505105
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- Ligue Nationale contre le Cancer (Equipe labellisee)
- Institut National du Cancer
- Institut National de la Sante et de la Recherche Medicale
- Association pour la Recherche contre le Cancer
- Ligue Nationale contre le Cancer, Spanish Ministry of Economy and Competitiveness [BFU2012-38146]
- Generalitat de Catalunya [2014-SGR-927]
- European Research Council [StG-242993, CoG-616480]
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/ 13-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.
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