title: WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion.
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.
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: García
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ragazzini
authors.affiliation: The Beatson Institute for Cancer Research, Glasgow, UK.
authors.forename: Xinzi
authors.initials: X
authors.lastname: Yu
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Cuesta-García
authors.affiliation: Science and Technology Facilities Council, Rutherford Appleton Laboratory, Central Laser Facility, Research Complex at Harwell, Harwell-Oxford, UK.
authors.forename: Jorge
authors.initials: J
authors.lastname: Bernardino de la Serna
authors.affiliation: The Beatson Institute for Cancer Research, Glasgow, UK.
authors.forename: Tobias
authors.initials: T
authors.lastname: Zech
authors.affiliation: Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sarrió
authors.affiliation: The Beatson Institute for Cancer Research, Glasgow, UK.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
authors.forename: Inés M
authors.initials: IM
authors.lastname: Antón
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D051356:Cortactin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008840:Microfilament Proteins; D009361:Neoplasm Invasiveness; D000069261:Podosomes / Q000378:metabolism*; D015398:Signal Transduction; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
chemical_list: C495868:CTTN protein, human; D002352:Carrier Proteins; D051356:Cortactin; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C495771:WASL protein, human; C109903:WIPF1 protein, human; C465744:WIPF2 protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal