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  • Title: WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion.
    Author: García E, Ragazzini C, Yu X, Cuesta-García E, Bernardino de la Serna J, Zech T, Sarrió D, Machesky LM, Antón IM.
    Journal: Sci Rep; 2016 Mar 24; 6():23590. PubMed ID: 27009365.
    Abstract:
    Cancer cells form actin-rich degradative protrusions (invasive pseudopods and invadopodia), which allows their efficient dispersal during metastasis. 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.
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