Rho-kinase inhibitor upregulates migration by altering focal adhesion formation via the Akt pathway in colon cancer cells

被引：31

作者：

Adachi, Seiji ^{[1
,2
]}

Yasuda, Ichiro ^{[2
]}

Nakashima, Masanori ^{[2
]}

Yamauchi, Takahiro ^{[2
]}

Yoshioka, Takashi ^{[3
]}

Okano, Yukio ^{[3
]}

Moriwaki, Hisataka ^{[2
]}

Kozawa, Osamu ^{[1
]}

机构：

[1] Gifu Univ, Grad Sch Med, Dept Pharmacol, Gifu 5011194, Japan

[2] Gifu Univ, Grad Sch Med, Dept Gastroenterol, Gifu 5011194, Japan

[3] Gifu Univ, Grad Sch Med, Dept Mol Pathobiochem, Gifu 5011194, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2011年 / 650卷 / 01期

关键词：

Rho-kinase; Cell migration; Colon cancer; Focal adhesion; Akt; ENDOTHELIAL GROWTH-FACTOR; STRESS FIBERS; (-)-EPIGALLOCATECHIN GALLATE; FACTOR RECEPTOR; EGF RECEPTOR; INVASION; ACTIVATION; GTPASES; PHOSPHORYLATION; TRANSFORMATION;

D O I：

10.1016/j.ejphar.2010.10.014

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Although Rho-kinase is reportedly implicated in carcinogenesis and the progression of human cancers its precise mechanism has not been fully elucidated We recently reported that Rho kinase negatively regulates epidermal growth factor (EGF) stimulated cancer progression in SW480 colon cancer cells In the present study we investigated the effect of Rho-kinase on the migration of SW480 colon cancer cells and the mechanism underlying the involvement of Rho-kinase Interestingly (R)-(+)-trans-N-(1-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide 2HCl (Y27632) a specific inhibitor of Rho kinase dose dependently enhanced cell migration SW480 cells spontaneously release vascular endothelial growth factor (VEGF) however Y27632 had little effect on its release While Rho-kinase which is generally phosphorylated in unstimulated cells was clearly suppressed by Y27632 exogenous VEGF did not affect its phosphorylation Immunofluorescence microscopy revealed that Y27632 caused a dramatic change in the localization of focal adhesion components vinculin phosphorylated caveolin-1 and tyrosine-phosphorylated proteins in SW480 cells Furthermore Ala inhibitor restored the loss of vinculin-stained focal adhesion formation induced by Y27632 We also observed similar effects for Y27632 on the migration and localization of focal adhesion components such as vinculin in another colon cancer cell line HT29 Taken together these results strongly suggest that Rho kinase negatively regulates the migration of colon cancer cells by altering focal adhesion formation via the Akt pathway (C) 2010 Elsevier B V All rights reserved

引用

页码：145 / 150

页数：6

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