Inhibition of farnesyltransferase reduces angiogenesis by interrupting endothelial cell migration

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• 作者：Guoyuan Peng¹ ; Yuan Ren¹ ; Xiaodong Sun ; Jun Zhou ; Dengwen Li ; ^{dwli@nankai.edu.cn}
• 关键词：Farnesyltransferase ; Angiogenesis ; Migration ; Endothelial cell ; Microtubule
• 刊名：Biochemical Pharmacology
• 出版年：2012
• 期刊代码：2_00062952
• 类别：pha
• 出版时间：15 May, 2012
• 卷：83
• 期：10
• 页码：1374-1382
• 文件大小：1892 K

摘要

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.