title: The Arp2/3 activator WASH regulates α5β1-integrin-mediated invasive migration.
abstract: The actin cytoskeleton provides scaffolding and physical force to effect fundamental processes such as motility, cytokinesis and vesicle trafficking. The Arp2/3 complex nucleates actin structures and contributes to endocytic vesicle invagination and trafficking away from the plasma membrane. Internalisation and directed recycling of integrins are major driving forces for invasive cell motility and potentially for cancer metastasis. Here, we describe a direct requirement for WASH and Arp2/3-mediated actin polymerisation on the endosomal membrane system for α5β1 integrin recycling. WASH regulates the trafficking of endosomal α5β1 integrin to the plasma membrane and is fundamental for integrin-driven cell morphology changes and integrin-mediated cancer cell invasion. Thus, we implicate WASH and Arp2/3-driven actin nucleation in receptor recycling leading to invasive motility.
authors: Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD,  UK.
authors: Tobias
authors: T
authors: Zech
authors: Simon D J
authors: SD
authors: Calaminus
authors: Patrick
authors: P
authors: Caswell
authors: Heather J
authors: HJ
authors: Spence
authors: Michael
authors: M
authors: Carnell
authors: Robert H
authors: RH
authors: Insall
authors: Jim
authors: J
authors: Norman
authors: Laura M
authors: LM
authors: Machesky
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D021381:Protein Transport; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D039081:Integrin alpha5beta1; D051316:Wiskott-Aldrich Syndrome Protein