Faculty Opinions recommendation of Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells.

Author(s):  
Jocelyn McDonald

2016 ◽  
Vol 212 (2) ◽  
pp. 199-217 ◽  
Author(s):  
Cédric Plutoni ◽  
Elsa Bazellieres ◽  
Maïlys Le Borgne-Rochet ◽  
Franck Comunale ◽  
Agusti Brugues ◽  
...  

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.



2014 ◽  
Vol 16 (3) ◽  
pp. 217-223 ◽  
Author(s):  
M. Reffay ◽  
M. C. Parrini ◽  
O. Cochet-Escartin ◽  
B. Ladoux ◽  
A. Buguin ◽  
...  


2014 ◽  
Vol 16 (4) ◽  
pp. 382-382
Author(s):  
M. Reay ◽  
M. C. Parrini ◽  
O. Cochet-Escartin ◽  
B. Ladoux ◽  
A. Buguin ◽  
...  


Author(s):  
Naoya Hino ◽  
Leone Rossetti ◽  
Ariadna Marín-Llauradó ◽  
Kazuhiro Aoki ◽  
Xavier Trepat ◽  
...  

AbstractDuring collective migration of epithelial cells, the migration direction is aligned over a large, tissue-scale expanse. Although the collective cell migration is known to be directed by mechanical forces transmitted via cell-cell junctions, it remains elusive how the intercellular force transmission is coordinated with intracellular biochemical signaling to achieve collective movements. Here we show that intercellular coupling of extracellular signal-regulated kinase (ERK)-mediated mechanochemical feedback in individual cells yields long-distance transmission of guidance cues. Mechanical stretch activates ERK through epidermal growth factor receptor (EGFR) activation, and the ERK activation triggers cell contraction. In addition, the contraction of the activated cell pulls neighboring cells via cell-cell junctions, evoking another round of ERK activation and contraction in the neighbors. Furthermore, anisotropic contraction based on front-rear cell polarization guarantees unidirectional propagation of ERK activation waves, and in turn, the ERK activation waves direct multicellular alignment of the polarity, leading to long-range ordered migration. Our findings reveal that mechanical forces mediate intercellular signaling underlying sustained transmission of guidance cues for collective cell migration.



Sign in / Sign up

Export Citation Format

Share Document