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

Mirvat El-Sibai, Peri Nalbant, Huan Pang, Rory J. Flinn, Corina Sarmiento, Frank P. Macaluso, Michael Cammer, John S. Condeelis, Klaus M. Hahn, Jonathan M. Backer

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 EGF-stimulated protrusion and reduced cell motility in time-lapse 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.

Original languageEnglish (US)
Pages (from-to)3465-3474
Number of pages10
JournalJournal of Cell Science
Volume120
Issue number19
DOIs
StatePublished - Oct 1 2007

Fingerprint

Epidermal Growth Factor
Carcinoma
Actin Cytoskeleton
Cell Movement
Cell Polarity
Phosphatidylinositol 3-Kinases
Polymerization
Electron Scanning Microscopy
Small Interfering RNA
Actins
Membranes

Keywords

  • Arp2/3
  • Cdc42
  • EGF
  • Metastasis
  • WAVE2

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells. / El-Sibai, Mirvat; Nalbant, Peri; Pang, Huan; Flinn, Rory J.; Sarmiento, Corina; Macaluso, Frank P.; Cammer, Michael; Condeelis, John S.; Hahn, Klaus M.; Backer, Jonathan M.

In: Journal of Cell Science, Vol. 120, No. 19, 01.10.2007, p. 3465-3474.

Research output: Contribution to journalArticle

El-Sibai, M, Nalbant, P, Pang, H, Flinn, RJ, Sarmiento, C, Macaluso, FP, Cammer, M, Condeelis, JS, Hahn, KM & Backer, JM 2007, 'Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells', Journal of Cell Science, vol. 120, no. 19, pp. 3465-3474. https://doi.org/10.1242/jcs.005942
El-Sibai, Mirvat ; Nalbant, Peri ; Pang, Huan ; Flinn, Rory J. ; Sarmiento, Corina ; Macaluso, Frank P. ; Cammer, Michael ; Condeelis, John S. ; Hahn, Klaus M. ; Backer, Jonathan M. / Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells. In: Journal of Cell Science. 2007 ; Vol. 120, No. 19. pp. 3465-3474.
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