Involvement of Rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells

被引:128
作者
Li, Bo [1 ]
Zhao, Wei-Dong [1 ]
Tan, Zhi-Min [1 ]
Fang, Wen-Gang [1 ]
Zhu, Li [1 ]
Chen, Yu-Hua [1 ]
机构
[1] China Med Univ, Minist Publ Hlth China, Key Lab Cell Biol, Dept Dev Biol, Shenyang 110001, Liaoning, Peoples R China
关键词
small cell lung cancer; Rho/ROCK; brain; endothelial cell; tight junction;
D O I
10.1016/j.febslet.2006.06.056
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Small cell lung cancer (SCLC) cells migration across human brain microvascular endothelial cells (HBMECs) is an essential step of brain metastases. Here we investigated signalling pathways in HBMECs contributing to the process. Inhibition of endothelial Rho kinase (ROCK) with Y27632 and overexpression of ROCK dominant-negative mutant prevented SCLC cells, NCI-H209, transendothelial migration and the concomitant changes of tight junction. Conversely, inhibition of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) had no effects. Furthermore, endothelial RhoA protein was activated during NCI-H209 cells transendothelial migration. Rho/ROCK participated in NCI-H209 cells transendothelial migration through regulating actin cytoskeleton reorganization. These results suggested that Rho/ROCK was required for SCLC cells transendothelial migration. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:4252 / 4260
页数:9
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