Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells

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dc.contributor.author El-Sibai, Mirvat
dc.contributor.author Nalbant, Peri
dc.contributor.author Pang, Huan
dc.contributor.author Flinn, Rory J.
dc.contributor.author Sarmiento, Corina
dc.contributor.author Macaluso, Frank
dc.contributor.author Cammer, Michael
dc.contributor.author Condeelis, John S.
dc.contributor.author Hahn, Klaus M.
dc.contributor.author Backer, Jonathan M.
dc.date.accessioned 2015-11-09T08:30:19Z
dc.date.available 2015-11-09T08:30:19Z
dc.date.copyright 2007-10-01
dc.date.issued 2015-11-09
dc.identifier.issn 0021-9533 en_US
dc.identifier.uri http://hdl.handle.net/10725/2492
dc.description.abstract Cdc42 plays a central role in regulating the actin cytoskeleton and maintaining cell polarity. Here, we show that Cdc42 is crucial for epidermal growth factor (EGF)- stimulated protrusion in MTLn3 carcinoma cells. When stimulated with EGF, carcinoma cells showed a rapid increase in activated Cdc42 that is primarily localized to the protruding edge of the cells. siRNA-mediated knockdown of Cdc42 expression caused a decrease in EGFstimulated protrusion and reduced cell motility in timelapse studies. These changes were correlated with a decrease in barbed-end formation and Arp2/3 localization at the cell edge, and a marked defect in actin filament branching, as revealed by rotary-shadowing scanning electron microscopy. Upstream of Arp2/3, Cdc42 knockdown inhibited EGF-stimulated activation of PI 3- kinase at early (within 1 minute) but not late (within 3 minutes) time points. Membrane targeting of N-WASP, WAVE2 and IRSp53 were also inhibited. Effects on WAVE2 were not owing to Rac1 inhibition, because WAVE2 recruitment is unaffected by Rac1 knockdown. Our data suggest that Cdc42 activation is crucial for the regulation of actin polymerization in carcinoma cells, and required for both EGF-stimulated protrusion and cell motility independently of effects on Rac. en_US
dc.language.iso en en_US
dc.title Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 200703859 en_US
dc.author.woa N/A en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Journal of Cell Science en_US
dc.journal.volume 120 en_US
dc.journal.issue 19 en_US
dc.article.pages 3465-3474 en_US
dc.keywords Cdc42 en_US
dc.keywords Arp2/3 en_US
dc.keywords WAVE2 en_US
dc.keywords EGF en_US
dc.keywords Metastasis en_US
dc.identifier.doi http://dx.doi.org/10.1242/jcs.005942 en_US
dc.identifier.ctation El-Sibai, M., Nalbant, P., Pang, H., Flinn, R. J., Sarmiento, C., Macaluso, F., ... & Backer, J. M. (2007). Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells. Journal of cell science, 120(19), 3465-3474. en_US
dc.author.email mirvat.elsibai@lau.edu.lb
dc.identifier.url http://jcs.biologists.org/content/120/19/3465
dc.orcid.id https://orcid.org/0000-0003-4084-6759 en_US

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