A direct interaction between fascin and microtubules contributes to adhesion dynamics and cell migration

Author:

Villari Giulia1,Jayo Asier1,Zanet Jennifer12,Fitch Briana1,Serrels Bryan3,Frame Margaret3,Stramer Brian M.1,Goult Benjamin T.4,Parsons Maddy1

Affiliation:

1. Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London SE1 1UL, UK

2. Université de Toulouse, Université Paul Sabatier and Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5547, Centre de Biologie du Développement, F-31062 Toulouse, France

3. Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, UK

4. School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, UK

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) 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 may have implications for the design of therapies to target fascin in metastatic disease.

Publisher

The Company of Biologists

Subject

Cell Biology

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