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CdGAP regulates cell migration and adhesion dynamics in two‐and three‐dimensional matrix environments
Author(s) -
Wormer Duncan,
Deakin Nicholas O.,
Turner Christopher E.
Publication year - 2012
Publication title -
cytoskeleton
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.95
H-Index - 86
eISSN - 1949-3592
pISSN - 1949-3584
DOI - 10.1002/cm.21057
Subject(s) - cdc42 , lamellipodium , microbiology and biotechnology , biology , rac1 , cell migration , adhesion , cell adhesion , focal adhesion , gene silencing , gtpase , matrix (chemical analysis) , cell , signal transduction , chemistry , biochemistry , gene , organic chemistry , chromatography
CdGAP is a Rac1/Cdc42 specific GTPase activating protein (GAP) that localizes to cell–matrix adhesions through an interaction with the adhesion scaffold α‐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. © 2012 Wiley Periodicals, Inc.