title: Inhibition of farnesyltransferase reduces angiogenesis by interrupting endothelial cell migration.
abstract: 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 FTase in angiogenesis and showed that FTI inhibited angiogenesis by directly acting on endothelial cells. Inhibition of FTase 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 FTase 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 FTase in endothelial cells and provide valuable information for the use of FTI in cancer therapy.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Guoyuan
authors.initials: G
authors.lastname: Peng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
mesh_terms: D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D016133:Polymerase Chain Reaction
chemical_list: D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase