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 proor 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 β3dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control their migration. β3integrin 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 β3-integrin levels are reduced.