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

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

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)615-630
Number of pages16
JournalCancer Cell
Volume22
Issue number5
DOIs
StatePublished - Nov 13 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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