Differential Remodeling of Actin Cytoskeleton Architecture by Profilin Isoforms Leads to Distinct Effects on Cell Migration and Invasion
Author(s)Mouneimne, Ghassan; Hansen, Scott D.; Selfors, Laura M.; Petrak, Lara; Hickey, Michele M.; Gallegos, Lisa L.; Simpson, Kaylene J.; Lim, James; Gertler, Frank; Hartwig, John H.; Mullins, R. Dyche; Brugge, Joan S.; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MIT
Mouneimne, Ghassan, Scott D. Hansen, Laura M. Selfors, Lara Petrak, Michele M. Hickey, Lisa L. Gallegos, Kaylene J. Simpson, et al. “Differential Remodeling of Actin Cytoskeleton Architecture by Profilin Isoforms Leads to Distinct Effects on Cell Migration and Invasion.” Cancer Cell 22, no. 5 (November 2012): 615-630. Copyright © 2012 Elsevier Inc.
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