title: A direct interaction between fascin and microtubules contributes to adhesion dynamics and cell migration.
abstract: Fascin is an actin-binding and bundling protein that is highly upregulated in most epithelial cancers. Fascin promotes cell migration and adhesion dynamics in vitro and tumour cell metastasis in vivo. However, potential non-actin bundling roles for fascin remain unknown. Here, we show for the first time that fascin can directly interact with the microtubule cytoskeleton and that this does not depend upon fascin-actin bundling. Microtubule binding contributes to fascin-dependent control of focal adhesion dynamics and cell migration speed. We also show that fascin forms a complex with focal adhesion kinase (FAK, also known as PTK2) and Src, and that this signalling pathway lies downstream of fascin-microtubule association in the control of adhesion stability. These findings shed light on new non actin-dependent roles for fascin and might have implications for the design of therapies to target fascin in metastatic disease.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London SE1 1UL, UK.
authors.forename: Giulia
authors.initials: G
authors.lastname: Villari
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London SE1 1UL, UK.
authors.forename: Asier
authors.initials: A
authors.lastname: Jayo
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London SE1 1UL, UK Université de Toulouse, Université Paul Sabatier and Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5547, Centre de Biologie du Développement, Toulouse F-31062, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zanet
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London SE1 1UL, UK.
authors.forename: Briana
authors.initials: B
authors.lastname: Fitch
authors.affiliation: Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, UK.
authors.forename: Bryan
authors.initials: B
authors.lastname: Serrels
authors.affiliation: Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Frame
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London SE1 1UL, UK.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Stramer
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Goult
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London SE1 1UL, UK maddy.parsons@kcl.ac.uk.
authors.forename: Maddy
authors.initials: M
authors.lastname: Parsons
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; C020324:fascin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: Actin; Cytoskeleton; Fascin; Focal adhesion; Focal adhesion kinase; Microtubule; Migration