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

García, E., Ragazzini, C., Yu, X., Cuesta-García, E., Bernardino de la Serna, J., Zech, T., Sarrió, D., Machesky, L. M. and Antón, I. M. (2016) WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion. Scientific Reports, 6, 23590. (doi: 10.1038/srep23590) (PMID:27009365) (PMCID:PMC4806363)

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: Articles
• Additional Information: EG held a contract from the Comunidad Autónoma de Madrid (CAM) and short-term fellowships from EMBO and CSIC. JBdlS is funded by a Marie Curie Career Integration Grant, LMM by Cancer Research UK, and IMA by the Spanish Ministry of Science and Innovation (SAF2013-45937-R) and by CIBERNED (Instituto de Salud Carlos III).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Zech, Mr Tobias and Yu, Miss Xinzi and Machesky, Professor Laura
• Authors: García, E., Ragazzini, C., Yu, X., Cuesta-García, E., Bernardino de la Serna, J., Zech, T., Sarrió, D., Machesky, L. M., and Antón, I. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Scientific Reports
• Publisher: Nature Publishing Group
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Published Online: 24 March 2016
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Scientific Reports 6: 23590
• Publisher Policy: Reproduced under Creative Commons License