AbstractThe physical interactions of cells with their external environment are critical for their survival and function. These interactions are altered upon epithelial to mesenchymal transition (EMT) as cells switch from relying primarily on cell-cell adhesions to relying on cell-matrix adhesions. Mechanical signals are central to regulating these two types of interactions, but the crosstalk and the mechanobiological processes that mediate the transition between them are poorly understood. Here we show that α-catenin, a mechanosensitive protein that regulates cadherin-based cell-cell adhesions, directly interacts with integrin adhesions and regulates their growth as well as their transmission of mechanical forces into the matrix. In mesenchymal cells, α-catenin is recruited to the cell edge where it interacts with actin in regions devoid of α-actinin. As actin and α-catenin flow from the cell edge toward the center, α-catenin interacts with vinculin within integrin adhesions to mediate adhesion maturation, enhance force transmission, and drive the proper assembly of actin stress fibers. Importantly, in the absence of α-catenin–vinculin interactions, cell adhesion to the matrix is impaired, and the cells display aberrant responses to matrix rigidity which is manifested in rigidity-independent growth. These results provide a novel understanding of α-catenin as having a dual-role in mechanosensing by both cell-cell and cell-matrix adhesions.
A PAK6–IQGAP1 complex promotes disassembly of cell–cell adhesions
