ADAM15 suppresses cell motility by driving integrin alpha 5 beta 1 cell surface expression via Erk inactivation

doi:10.1016/j.bioce1.2008.02.021

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	ADAM15 suppresses cell motility by driving integrin alpha 5 beta 1 cell surface expression via Erk inactivation
	Chen, Qin; Meng, Ling-hua; Zhu, Cai-hua; Lin, Li-ping; Lu, He; Ding, Jian
刊名	INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
	2008
卷号	40 期号:10 页码:2164-2173
关键词	ADAM15 integrin Erk1/2 migration metastasis
ISSN号	1357-2725
DOI	10.1016/j.bioce1.2008.02.021
文献子类	Article
英文摘要	Human ADAM15 is unique among the A disintegrin and metalloprotease domain (ADAM) family because of the integrin binding motif Arg-Gly-Asp (RGD) within its disintegrin domain. Integrin alpha 5 beta 1 has been reported to bind to ADAM15 in an RGD-dependent manner, but the biological significance of the interaction between ADAM15 and alpha 5 beta 1 is unknown. To characterize the effects of ADAM15 on alpha 5 beta 1-mediated cell adhesion and migration and elucidate the potential mechanism, CHO cells which express endogenous integrin alpha 5 beta 1 were transfected with human ADAM15 cDNA. ADAM15 overexpression led to enhanced cell adhesion and decreased migration on fibronectin, which were suppressed by down-regulation of integrin alpha 5. Overexpression of ADAM15 not only increased the cell surface expression of integrin alpha 5 but also resulted in a more clustered staining of alpha 5 on cell surface, while the beta 1 subunit remained unchanged. Unexpectedly, results from immunoprecipitation and immunofluorescence indicated that ADAM15 and alpha 5 beta 1 integrin did not interact directly in CHO cells. We found that ADAM15 expression decreased the phosphorylation of Erk1/2. Consistently, down-regulation of Erk1/2 phosphorylation by MEK inhibitor PD98059 or siRNA against Erk1/2 enhanced the expression of alpha 5 on cell surface. By using a B16F10 pulmonary metastasis model, we revealed that overexpression of ADAM15 significantly reduced the number of metastatic nodules on the lung. Taken together, this study reveals for the first time that ADAM15 could drive alpha 5 integrin expression on cell surface via down-regulation of phosphorylated Erk1/2. This presents a novel mechanism by which ADAM15 regulates cell-matrix adhesion and migration. (C) 2008 Elsevier Ltd. All rights reserved.
WOS关键词	DISINTEGRIN ; PROTEIN ; METARGIDIN ; DOMAIN ; ADHESION ; ADAM-15 ; BINDING ; CANCER ; ALPHA-V-BETA-3 ; ALPHA-5-BETA-1
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000258479700022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273043]
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	Lu, He
作者单位	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	Chen, Qin,Meng, Ling-hua,Zhu, Cai-hua,et al. ADAM15 suppresses cell motility by driving integrin alpha 5 beta 1 cell surface expression via Erk inactivation[J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2008,40(10):2164-2173.
APA	Chen, Qin,Meng, Ling-hua,Zhu, Cai-hua,Lin, Li-ping,Lu, He,&Ding, Jian.(2008).ADAM15 suppresses cell motility by driving integrin alpha 5 beta 1 cell surface expression via Erk inactivation.INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,40(10),2164-2173.
MLA	Chen, Qin,et al."ADAM15 suppresses cell motility by driving integrin alpha 5 beta 1 cell surface expression via Erk inactivation".INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 40.10(2008):2164-2173.