Both embryonic development and cancer cell invasion require coordinated directional collective cell migration (DCCM). Two key aspects of this process are force transmission of traction forces from collectively migrating cells to the extracellular matrix (ECM) and mechanosignalling at cell–cell contact sites. P-cadherin promotes DCCM through activation of the β-Pix–CDC42 polarity pathway, which gauges intercellular tension and stress. It is poorly understood how forces to the ECM connect to cadherin-mediated mechanical cell–cell signalling. Now, Cécile Gauthier-Rouviére and colleagues (Le Borgne-Rochet et al., 2019) address the role of P-cadherin in DCCM and find that the collagen-remodelling proteoglycan decorin is expressed and secreted upon expression of P-cadherin in mesenchymal cells such as myoblasts, which align collagen fibres in the direction of migration in a decorin-dependent manner. This alignment is also observed in breast cancer cells at invasion sites when both factors are expressed. Specifically, decorin participates in the P-cadherin-mediated increase in traction force strength, force anisotropy and β1 integrin and β-Pix–CDC42 activation. This work describes a new mechanism that drives DCCM through ECM remodelling and collagen fibre alignment based on cadherin-mediated mechanical coupling signalling.
-PolarityCFP.png?versionId=4491)
-HUBSwebinar.jpg?versionId=4491)
