Author/Authors :
Mouneimne، نويسنده , , Ghassan and Hansen، نويسنده , , Scott D. and Selfors، نويسنده , , Laura M. and Petrak، نويسنده , , Lara and Hickey، نويسنده , , Michele M. and Gallegos، نويسنده , , Lisa L. and Simpson، نويسنده , , Kaylene J. and Lim، نويسنده , , James and Gertler، نويسنده , , Frank B. and Hartwig، نويسنده , , John H. and Mullins، نويسنده , , R. Dyche and Brugge، نويسنده , , Joan S.، نويسنده ,
Abstract :
Summary
c actin cytoskeletal reorganization is integral to cell motility. Profilins are well-characterized regulators of actin polymerization; however, functional differences among coexpressed profilin isoforms are not well defined. Here, we demonstrate that profilin-1 and profilin-2 differentially regulate membrane protrusion, motility, and invasion; these processes are promoted by profilin-1 and suppressed by profilin-2. Compared to profilin-1, profilin-2 preferentially drives actin polymerization by the Ena/VASP protein, EVL. Profilin-2 and EVL suppress protrusive activity and cell motility by an actomyosin contractility-dependent mechanism. Importantly, EVL or profilin-2 downregulation enhances invasion in vitro and in vivo. In human breast cancer, lower EVL expression correlates with high invasiveness and poor patient outcome. We propose that profilin-2/EVL-mediated actin polymerization enhances actin bundling and suppresses breast cancer cell invasion.
