1. Differential remodeling of actin cytoskeleton architecture by profilin isoforms leads to distinct effects on cell migration and invasion.
- Author
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Mouneimne G, Hansen SD, Selfors LM, Petrak L, Hickey MM, Gallegos LL, Simpson KJ, Lim J, Gertler FB, Hartwig JH, Mullins RD, and Brugge JS
- Subjects
- Actin Cytoskeleton ultrastructure, Breast Neoplasms metabolism, Breast Neoplasms pathology, Breast Neoplasms ultrastructure, Cell Adhesion Molecules metabolism, Cell Adhesion Molecules physiology, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, MCF-7 Cells, Myosins metabolism, Myosins physiology, Neoplasm Grading, Neoplasm Invasiveness genetics, Neoplasms genetics, Neoplasms metabolism, Profilins metabolism, Protein Isoforms metabolism, Protein Isoforms physiology, RNA Interference, Actin Cytoskeleton metabolism, Cell Movement, Neoplasms pathology, Profilins physiology
- 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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