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New microtubulin inhibitor MT189 suppresses angiogenesis via the JNK-VEGF/VEGFR2 signaling axis

文献类型：期刊论文

作者Xu, Lin1,3; Wang, Wei3; Meng, Tao2; Ma, Lan-Ping2; Tong, Lin-Jiang3; Shen, Jing-Kang2; Wang, Ying-Qing3; Miao, Ze-Hong3
刊名CANCER LETTERS
出版日期2018-03-01
卷号416页码:57-65
关键词MT189 Microtubulin inhibitor VEGF Src JNK Cell adhesion
ISSN号0304-3835
DOI10.1016/j.canlet.2017.12.022
文献子类Article
英文摘要The microtubulin inhibitor MT189 possesses anticancer activity and has been shown to overcome multidrug resistance. Here, we report that MT189 also inhibits angiogenesis. MT189 inhibited the proliferation, migration and differentiation of endothelial cells, with or without VEGF stimulation, and suppressed microvessel formation ex vivo and in vivo. MT189 reduced VEGF expression and secretion in both tumor and endothelial cells, under either hypoxic or normoxic conditions. The activation of VEGFR2 and downstream Src was thus abrogated in the MT189-treated endothelial cells. MT189 subsequently stabilized endothelial cell-cell junctions consist of VE-cadherin, beta-catenin, vinculin, and actin. MT189 also disrupted endothelial cell-matrix junctions by inhibiting the turnover of focal adhesions containing FAK, paxillin, vinculin, and actin. Inhibition of JNK reversed MT189-mediated inhibition of endothelial migration and differentiation, JNK activation, the reduction of VEGF expression and secretion, and the decrease of Src and FAK phosphorylation. These results indicate that MT189 suppresses angiogenesis by reducing endothelial proliferation, migration, and differentiation via the JNK-VEGF/VEGFR2 signaling axis. Together with our previous report showing that MT189 exhibited anticancer activity via the JNK-MCL-1 pathway, these new findings further support MT189-based drug development for cancer therapy. (C) 2017 Elsevier B.V. All rights reserved.
WOS关键词TUBULIN POLYMERIZATION ; ANTICANCER ACTIVITY ; MECHANOTRANSDUCTION ; PROLIFERATION ; PERMEABILITY ; DEGRADATION ; MECHANISMS ; AGENTS
资助项目National Natural Science Foundation of China[81202548] ; Chinese Academy of Sciences[00000000]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000424717500006
出版者ELSEVIER IRELAND LTD
源URL[http://119.78.100.183/handle/2S10ELR8/279884]  
专题药理学第一研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Wang, Ying-Qing; Miao, Ze-Hong
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Xu, Lin,Wang, Wei,Meng, Tao,et al. New microtubulin inhibitor MT189 suppresses angiogenesis via the JNK-VEGF/VEGFR2 signaling axis[J]. CANCER LETTERS,2018,416:57-65.
APA Xu, Lin.,Wang, Wei.,Meng, Tao.,Ma, Lan-Ping.,Tong, Lin-Jiang.,...&Miao, Ze-Hong.(2018).New microtubulin inhibitor MT189 suppresses angiogenesis via the JNK-VEGF/VEGFR2 signaling axis.CANCER LETTERS,416,57-65.
MLA Xu, Lin,et al."New microtubulin inhibitor MT189 suppresses angiogenesis via the JNK-VEGF/VEGFR2 signaling axis".CANCER LETTERS 416(2018):57-65.

入库方式： OAI收割

来源：上海药物研究所

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