Updated project metadata. Integrin ??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 ??3???s role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the ??3-dependent adhesome. We show that depletion of ??3-integrin in this cell type leads to changes in microtubule behaviour that control their migration. ??3-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 ??3-integrin levels are reduced.