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bioRxiv · 10.1101/145839

The β3-integrin endothelial adhesome regulates microtubule dependent cell migration

Atkinson, S. J.·Gontarczyk, A. M.·Ellison, T. S.·Johnson, R. T.·Kirkup, B. M.·Alghamdi, A.·Fowler, W. J.·Silva, B. C.·Schneider, J. J.·Weilbaecher, K. N.·Mogensen, M. M.·Bass, M. D.·Edwards, D. R.·Robinson, S. D.
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Abstract

Integrin {beta}3 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 {beta}3s role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the {beta}3- dependent adhesome. We show that depletion of {beta}3-integrin in this cell type leads to changes in microtubule behaviour that control their migration. {beta}3- integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2 driven control of Rac1 activity. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when {beta}3-integrin levels are reduced.

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Atkinson, S. J., Gontarczyk, A. M., Ellison, T. S., Johnson, R. T., Kirkup, B. M., Alghamdi, A., Fowler, W. J., Silva, B. C., Schneider, J. J., Weilbaecher, K. N., Mogensen, M. M., Bass, M. D., Edwards, D. R., Robinson, S. D.. 2017-06-03. The β3-integrin endothelial adhesome regulates microtubule dependent cell migration. https://doi.org/10.1101/145839

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