Differential Remodeling of Actin Cytoskeleton Architecture by Profilin Isoforms Leads to Distinct Effects on Cell Migration and Invasion
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Gertler_Differential remodeling.pdf
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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.
Date Issued
November 2012
Journal
Cancer Cell
Publisher
Elsevier
Citation
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.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.ccr.2012.09.027
