Document Detail


Transducer of Cdc42-dependent actin assembly promotes epidermal growth factor-induced cell motility and invasiveness.
MedLine Citation:
PMID:  21062739     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Toca-1 (transducer of Cdc42-dependent actin assembly) interacts with the Cdc42·N-WASP and Abi1·Rac·WAVE F-actin branching pathways that function in lamellipodia formation and cell motility. However, the potential role of Toca-1 in these processes has not been reported. Here, we show that epidermal growth factor (EGF) induces Toca-1 localization to lamellipodia, where it co-localizes with F-actin and Arp2/3 complex in A431 epidermoid carcinoma cells. EGF also induces tyrosine phosphorylation of Toca-1 and interactions with N-WASP and Abi1. Stable knockdown of Toca-1 expression by RNA interference has no effect on cell growth, EGF receptor expression, or internalization. However, Toca-1 knockdown cells display defects in EGF-induced filopodia and lamellipodial protrusions compared with control cells. Further analyses reveal a role for Toca-1 in localization of Arp2/3 and Abi1 to lamellipodia. Toca-1 knockdown cells also display a significant defect in EGF-induced motility and invasiveness. Taken together, these results implicate Toca-1 in coordinating actin assembly within filopodia and lamellipodia to promote EGF-induced cell migration and invasion.
Authors:
Jinghui Hu; Alka Mukhopadhyay; Andrew W B Craig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-09
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-17     Completed Date:  2011-02-24     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2261-72     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and the Cancer Biology and Genetics Division, Queen's University Cancer Research Institute, Queen's University Kingston, Ontario K7L 3N6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Actin-Related Protein 2-3 Complex / genetics,  metabolism
Actins / genetics,  metabolism*
Adaptor Proteins, Signal Transducing / genetics,  metabolism
Carrier Proteins / genetics,  metabolism*
Cell Line
Cell Movement / drug effects,  physiology*
Cytoskeletal Proteins / genetics,  metabolism
Epidermal Growth Factor / metabolism*,  pharmacology
Gene Knockdown Techniques
Humans
Protein Transport / drug effects,  physiology
Pseudopodia / genetics,  metabolism
Wiskott-Aldrich Syndrome Protein / genetics,  metabolism
Wiskott-Aldrich Syndrome Protein Family / genetics,  metabolism
cdc42 GTP-Binding Protein / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/ABI1 protein, human; 0/Actin-Related Protein 2-3 Complex; 0/Actins; 0/Adaptor Proteins, Signal Transducing; 0/Carrier Proteins; 0/Cytoskeletal Proteins; 0/FNBP1L protein, human; 0/WAS protein, human; 0/WASF1 protein, human; 0/Wiskott-Aldrich Syndrome Protein; 0/Wiskott-Aldrich Syndrome Protein Family; 62229-50-9/Epidermal Growth Factor; EC 3.6.5.2/cdc42 GTP-Binding Protein
Comments/Corrections

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