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Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin.

Authors: Yamaguchi, Hideki  Lorenz, Mike  Kempiak, Stephan  Sarmiento, Corina  Coniglio, Salvatore  Symons, Marc  Segall, Jeffrey  Eddy, Robert  Miki, Hiroaki  Takenawa, Tadaomi  Condeelis, John 
Citation: Yamaguchi H, etal., J Cell Biol. 2005 Jan 31;168(3):441-52.
Pubmed: (View Article at PubMed) PMID:15684033
DOI: Full-text: DOI:10.1083/jcb.200407076

Invadopodia are actin-rich membrane protrusions with a matrix degradation activity formed by invasive cancer cells. We have studied the molecular mechanisms of invadopodium formation in metastatic carcinoma cells. Epidermal growth factor (EGF) receptor kinase inhibitors blocked invadopodium formation in the presence of serum, and EGF stimulation of serum-starved cells induced invadopodium formation. RNA interference and dominant-negative mutant expression analyses revealed that neural WASP (N-WASP), Arp2/3 complex, and their upstream regulators, Nck1, Cdc42, and WIP, are necessary for invadopodium formation. Time-lapse analysis revealed that invadopodia are formed de novo at the cell periphery and their lifetime varies from minutes to several hours. Invadopodia with short lifetimes are motile, whereas long-lived invadopodia tend to be stationary. Interestingly, suppression of cofilin expression by RNA interference inhibited the formation of long-lived invadopodia, resulting in formation of only short-lived invadopodia with less matrix degradation activity. These results indicate that EGF receptor signaling regulates invadopodium formation through the N-WASP-Arp2/3 pathway and cofilin is necessary for the stabilization and maturation of invadopodia.

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CRRD Object Information
CRRD ID: 11575050
Created: 2016-12-22
Species: All species
Last Modified: 2016-12-22
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.