WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion



Garcia, E, Ragazzini, C, Xinzi, Y, Cuesta-Garcia, E, Bernardino de la Serna, J, Zech, T ORCID: 0000-0001-8394-088X, Sarrio, D, Machesky, LM and Anton, IM
(2016) WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion. Scientific Reports, 6.

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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.

Item Type: Article
Uncontrolled Keywords: Actin, Breast cancer, Invadopodia
Depositing User: Symplectic Admin
Date Deposited: 06 Apr 2016 10:04
Last Modified: 16 Apr 2021 11:13
DOI: 10.1038/srep23590
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3000039