| First Author | Mouneimne G | Year | 2012 |
| Journal | Cancer Cell | Volume | 22 |
| Issue | 5 | Pages | 615-30 |
| PubMed ID | 23153535 | Mgi Jnum | J:205619 |
| Mgi Id | MGI:5545940 | Doi | 10.1016/j.ccr.2012.09.027 |
| Citation | Mouneimne G, et al. (2012) Differential remodeling of actin cytoskeleton architecture by profilin isoforms leads to distinct effects on cell migration and invasion. Cancer Cell 22(5):615-30 |
| abstractText | 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. |
