The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Samuel J. Atkinson, Aleksander M. Gontarczyk, Abdullah A.A. 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

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4 Scopus citations

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.

Original languageEnglish
Article numbere44578
JournalEMBO Reports
Volume19
Issue number7
DOIs
StatePublished - Jul 2018

Keywords

  • adhesome
  • endothelial
  • integrins
  • microtubules

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    Atkinson, S. J., Gontarczyk, A. M., Alghamdi, A. A. A., Ellison, T. S., Johnson, R. T., Fowler, W. J., Kirkup, B. M., Silva, B. C., Harry, B. E., Schneider, J. G., Weilbaecher, K. N., Mogensen, M. M., Bass, M. D., Parsons, M., Edwards, D. R., & Robinson, S. D. (2018). The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration. EMBO Reports, 19(7), [e44578]. https://doi.org/10.15252/embr.201744578