Inhibition of farnesyltransferase reduces angiogenesis by interrupting endothelial cell migration

Inhibitors of farnesyltransferase (FTI) have been developed for cancer treatment for more than a decade. Aside from being a therapeutic target in tumor cells, little is known about the role of farnesyltransferase (FTase) in other physiological processes. In this study, we revealed the involvement of Erase in angiogenesis and showed that FTI inhibited angiogenesis by directly acting on endothelial cells. Inhibition of Erase interrupted cell migration in vitro and in vivo. In addition, we found that FTase was important for cell polarization, cell spreading and pseudopodia formation. We also found that Erase interacted with microtubule end binding protein 1 (EB1) and that this interaction was critical for the localization of EB1 to microtubule tips. Our findings thus offer novel insight into the functions of Erase in endothelial cells and provide valuable information for the use of FTI in cancer therapy. (C) 2012 Elsevier Inc. All rights reserved.