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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\u2013Arp2\/3 pathway and cofilin is necessary for the stabilization and maturation of invadopodia.<\/jats:p>","DOI":"10.1083\/jcb.200407076","type":"journal-article","created":{"date-parts":[[2005,1,31]],"date-time":"2005-01-31T16:33:07Z","timestamp":1107189187000},"page":"441-452","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":627,"title":["Molecular mechanisms of invadopodium formation"],"prefix":"10.1083","volume":"168","author":[{"given":"Hideki","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"},{"name":"3Department of Cancer Genomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Lorenz","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kempiak","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Sarmiento","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Coniglio","sequence":"additional","affiliation":[{"name":"5Center for Oncology and Cell Biology, North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Symons","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"},{"name":"2Department of Surgery, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Segall","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Eddy","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Miki","sequence":"additional","affiliation":[{"name":"3Department of Cancer Genomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"},{"name":"6Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadaomi","family":"Takenawa","sequence":"additional","affiliation":[{"name":"4Department of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"},{"name":"7Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Condeelis","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,1,31]]},"reference":[{"key":"2023072215433367000_BIB1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1006\/excr.1998.4031","volume":"241","year":"1998","journal-title":"Exp. 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