Differential Remodeling of Actin Cytoskeleton Architecture by Profilin Isoforms Leads to Distinct Effects on Cell Migration and Invasion

作者：Mouneimne Ghassan; Hansen Scott D; Selfors Laura M; Petrak Lara; Hickey Michele M; Gallegos Lisa L; Simpson Kaylene J; Lim James; Gertler Frank B; Hartwig John H; Mullins R Dyche; Brugge Joan S^*

来源：Cancer Cell, 2012, 22(5): 615-630.

DOI：10.1016/j.ccr.2012.09.027

Dynamic 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.

• 出版日期2012-11-13