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J Biol Chem. 2011 Jan 21;286(3):2261-72. doi: 10.1074/jbc.M110.157974. Epub 2010 Nov 9.

Transducer of Cdc42-dependent actin assembly promotes epidermal growth factor-induced cell motility and invasiveness.

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1
Department of Biochemistry and the Cancer Biology and Genetics Division, Queen's University Cancer Research Institute, Queen's University Kingston, Ontario K7L 3N6, Canada.

Abstract

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.

PMID:
21062739
PMCID:
PMC3023521
DOI:
10.1074/jbc.M110.157974
[Indexed for MEDLINE]
Free PMC Article
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