The β3-integrin endothelial adhesome regulates microtubule dependent cell migration

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 their migration. β3- integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2 driven control of Rac1 activity. Our findings reveal that angiogenic processes, both and , are more sensitive to microtubule targeting agents when β3-integrin levels are reduced.