Cancer Cell
Volume 22, Issue 5, 13 November 2012, Pages 615-630
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Article
Differential Remodeling of Actin Cytoskeleton Architecture by Profilin Isoforms Leads to Distinct Effects on Cell Migration and Invasion

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Summary

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.

Highlights

► Profilin-2 preferentially drives EVL-mediated actin cytoskeletal remodeling ► Profilin-2 and EVL suppress protrusion, cell motility, and invasion ► Profilin-2 and EVL suppressive effects are dependent on actomyosin contractility ► Low EVL expression predicts poor patient outcome in breast cancer

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