The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration |
| |
| Authors: | Samuel J Atkinson Aleksander M Gontarczyk Abdullah AA Alghamdi Tim S Ellison Robert T Johnson Wesley J Fowler Benjamin M Kirkup Bernardo C Silva Bronwen E Harry Jochen G Schneider Katherine N Weilbaecher Mette M Mogensen Mark D Bass Maddy Parsons Dylan R Edwards Stephen D Robinson |
| |
| Institution: | 1. School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, UK;2. Luxembourg Center for Systems Biomedicine (LCSB), Luxembourg & Saarland University Medical Center, Internal Medicine II, University of Luxembourg, Homburg, Germany;3. Centre Hospitalier Emily Mayrisch, Esch, Luxembourg;4. Division of Molecular Oncology, Department of Internal Medicine, Washington University in St Louis, St. Louis, MO, USA;5. Department of Biomedical Science, Centre for Membrane Interactions and Dynamics, University of Sheffield, Sheffield, UK;6. Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guys Campus, London, UK;7. Faculty of Medicine and Health Sciences, Norwich Research Park, University of East Anglia, Norwich, UK |
| |
| Abstract: | Integrin β3 is seen as a key anti‐angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro‐ or anti‐angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3‐dependent adhesome. We show that depletion of β3‐integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3‐integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2‐driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3‐integrin levels are reduced. |
| |
| Keywords: | adhesome endothelial integrins microtubules |
|
|
