The ?3-integrin endothelial adhesome regulates microtubule-dependent cell migration.

ABSTRACT: 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 cell 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.

SUBMITTER: Atkinson SJ 

PROVIDER: S-EPMC6030693 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature