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Using biochemical and advanced imaging approaches, we demonstrate that the N-WASP-interactors WIP and WICH\/WIRE play non-redundant roles in cancer cell invasion. WIP interacts with N-WASP and cortactin and is essential for invadopodium assembly, whereas WICH\/WIRE regulates N-WASP activation to control invadopodium maturation and degradative activity. Our data also show that Nck interaction with WIP and WICH\/WIRE modulates invadopodium maturation; changes in WIP and WICH\/WIRE levels induce differential distribution of Nck. We show that WIP can replace WICH\/WIRE functions and that elevated WIP levels correlate with high invasiveness. These findings identify a role for WICH\/WIRE in invasiveness and highlight WIP as a hub for signaling molecule recruitment during invadopodium generation and cancer progression, as well as a potential diagnostic biomarker and an optimal target for therapeutic approaches.<\/jats:p>","DOI":"10.1038\/srep23590","type":"journal-article","created":{"date-parts":[[2016,3,24]],"date-time":"2016-03-24T06:50:01Z","timestamp":1458802201000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["WIP and WICH\/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion"],"prefix":"10.1038","volume":"6","author":[{"given":"Esther","family":"Garc\u00eda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ragazzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Cuesta-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Bernardino de la Serna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Zech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sarri\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Machesky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s M.","family":"Ant\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,24]]},"reference":[{"key":"BFsrep23590_CR1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrc1098","volume":"3","author":"IJ Fidler","year":"2003","unstructured":"Fidler, I. 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