Journal article
Differential Remodeling of Actin Cytoskeleton Architecture by Profilin Isoforms Leads to Distinct Effects on Cell Migration and Invasion
G Mouneimne, SD Hansen, LM Selfors, L Petrak, MM Hickey, LL Gallegos, KJ Simpson, J Lim, FB Gertler, JH Hartwig, RD Mullins, JS Brugge
Cancer Cell | CELL PRESS | Published : 2012
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 enh..
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Awarded by National Science Foundation
Funding Acknowledgements
We thank James Bui and Wa Xian for technical assistance; Rachel Davidowitz, Taru Muranen, and Scott Valastyan for their blinded analysis of the human tumor tissue arrays; the Nikon Imaging Center, particularly Jennifer Waters and Wendy Salmon; and the Rodent Histopathology Core Facility, particularly Roderick Bronson. This work was funded by the Breast Cancer Research Foundation, the NIGMS Cell Migration Consortium, a gift from the Lee Jeans Foundation through the Entertainment Industry Foundation (to J.S.B.); NIH Grant P01 HL059561 (to J.H.H.); NIH Grant ROI #GM61010, UCSF/UC Berkeley Nanomedicine Development Center and the National Science Foundation (to R.D.M. and S.D.H.); and NIH #GM58801 (to F.B.G.).