CdGAP regulates cell migration and adhesion dynamics in two-and three-dimensional matrix environments

CdGAP is a Rac1/Cdc42 specific GTPase activating protein (GAP) that localizes to cellmatrix adhesions through an interaction with the adhesion scaffold a-parvin/actopaxin to regulate lamellipodia formation and cell spreading. Herein, we demonstrate, using a combination of siRNA-mediated silencing and overexpression, that cdGAP negatively regulates directed and random migration by controlling adhesion maturation and dynamics through the regulation of both adhesion assembly and disassembly. Interestingly, cdGAP was also localized to adhesions formed in three-dimensional (3D) matrix environments and cdGAP depletion promoted cancer cell migration and invasion through 3D matrices. These findings highlight the importance of GAP proteins in the regulation of Rho family GTPases and the coordination of the cell migration machinery. (c) 2012 Wiley Periodicals, Inc.