RGD Reference Report - Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells. - Rat Genome Database

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

Authors: El-Sibai, M  Nalbant, P  Pang, H  Flinn, RJ  Sarmiento, C  Macaluso, F  Cammer, M  Condeelis, JS  Hahn, KM  Backer, JM 
Citation: El-Sibai M, etal., J Cell Sci. 2007 Oct 1;120(Pt 19):3465-74. Epub 2007 Sep 12.
RGD ID: 2306203
Pubmed: PMID:17855387   (View Abstract at PubMed)
PMCID: PMC4066376   (View Article at PubMed Central)
DOI: DOI:10.1242/jcs.005942   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cdc42Ratactin filament branching  IMP  RGD 
Baiap2Ratcellular response to epidermal growth factor stimulus  IEP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Actr3Ratcell leading edge  IDA  RGD 
Actr3Ratleading edge of lamellipodium  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Actr3  (actin related protein 3)
Baiap2  (BAR/IMD domain containing adaptor protein 2)
Cdc42  (cell division cycle 42)


Additional Information