title: WIP is necessary for matrix invasion by breast cancer cells.
abstract: Actin filament assembly and reorganisation during cell migration and invasion into extracellular matrices is a well-documented phenomenon. Among actin-binding proteins regulating its polymerisation, the members of the WASP (Wiskott Aldrich Syndrome Protein) family are generally thought to play the most significant role in supporting cell invasiveness. In situ, cytosolic N-WASP (neural WASP) is associated with a partner protein termed WIP (WASP Interacting Protein) that is bound to the N-terminal domain of N-WASP. Despite much effort, rather little is known about the role of WIP in regulating N-WASP and consequent actin-filament assembly. Even less is known about the function of WIP within the specialised cell adhesion and attachment structures known as podosomes and invadopodia. In particular, whilst the interaction of WIP with known participants in the development and maturation of invadopodia such as N-WASP, the Arp2/3 complex and cortactin has been described, little is known concerning the direct contribution of WIP to invadopodia and its potential role as a regulator of cancer cell invasion. In this report, we use 2D and 3D culture systems to describe the role played by WIP in modulating the morphology and invasiveness of metastatic breast cancer cells in vitro, as well as its effect on the process of mesenchymal-epithelial transition (MET) seen in these cells. We demonstrate that WIP is necessary for invadopodium formation and matrix degradation by basal breast cancer cells, but not sufficient to induce invasiveness in luminal cells.
authors.affiliation: Department of Cellular and Molecular Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus UAM Cantoblanco, Darwin 3, 28049 Madrid, Spain. Electronic address: eggonzalez@cnb.csic.es.
authors.forename: Esther
authors.initials: E
authors.lastname: García
authors.affiliation: The Beatson Institute for Cancer Research, Bearsden, Glasgow G61 1BD, Scotland, UK. Electronic address: Laura.Machesky@glasgow.ac.uk.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
authors.affiliation: Randall Division of Cell & Molecular Biophysics, King's College London, London SE1 1UL, UK. Electronic address: gareth.jones@kcl.ac.uk.
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Jones
authors.affiliation: Department of Cellular and Molecular Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus UAM Cantoblanco, Darwin 3, 28049 Madrid, Spain. Electronic address: ianton@cnb.csic.es.
authors.forename: Inés M
authors.initials: IM
authors.lastname: Antón
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness
chemical_list: D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C109903:WIPF1 protein, human
keywords: 3D invasion; Actin cytoskeleton; Epithelial–mesenchymal transition; Invadopodia; Matrix degradation; Metastasis