@article{27e278fb6e1f429aa92a8bae59d29424,
title = "Differential Remodeling of Actin Cytoskeleton Architecture by Profilin Isoforms Leads to Distinct Effects on Cell Migration and Invasion",
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.",
author = "Ghassan Mouneimne and Hansen, \{Scott D.\} and Selfors, \{Laura M.\} and Lara Petrak and Hickey, \{Michele M.\} and Gallegos, \{Lisa L.\} and Simpson, \{Kaylene J.\} and James Lim and Gertler, \{Frank B.\} and Hartwig, \{John H.\} and Mullins, \{R. Dyche\} and Brugge, \{Joan S.\}",
note = "Funding Information: 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.). ",
year = "2012",
month = nov,
day = "13",
doi = "10.1016/j.ccr.2012.09.027",
language = "English (US)",
volume = "22",
pages = "615--630",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}