Role of the hemopexin domain of matrix metalloproteinases in cell migration.
Role of the hemopexin domain of matrix metalloproteinases in cell migration.
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DOI：
10.1002/jcp.21535
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发表时间：
2008-12
影响因子：
5.6
通讯作者：
Cao, Jian
中科院分区：
文献类型：
--
作者：
Dufour, Antoine;Sampson, Nicole S.;Zucker, Stanley;Cao, Jian
The biological functions of matrix metalloproteinases (MMPs) extend beyond extracellular matrix degradation. Non-proteolytic activities of MMPs are just beginning to be understood. Herein, we evaluated the role of proMMPs in cell migration. Employing a Transwell chamber migration assay, we demonstrated that transfection of COS-1 cells with various proMMP cDNAs resulted in enhancement of cell migration. Latent MMP-2 and MMP-9 enhanced cell migration to a greater extent than latent MMP-1, -3, -11 and -28. To examine if proteolytic activity is required for MMP-enhanced cell migration, three experimental approaches, including fluorogenic substrate degradation assay, transfection of cells with catalytically inactive mutant MMP cDNAs, and addition of hydroxamic acid-derived MMP inhibitors, were employed. We demonstrated that the proteolytic activities of MMPs are not required for MMP-induced cell migration. To explore the mechanism underlying MMP-enhanced cell migration, structure-function relationship of MMP-9 on cell migration was evaluated. By using a domain swapping approach, we demonstrated that the hemopexin domain of proMMP-9 plays an important role in cell migration when examined by a transwell chamber assay and by a phagokinetic migration assay. TIMP-1, which interacts with the hemopexin domain of proMMP-9, inhibited cell migration, whereas TIMP-2 had no effect. Employing small molecular inhibitors, MAPK and PI3K pathways were found to be involved in MMP-9-mediated cell migration. In conclusion, we demonstrated that MMPs utilize a non-proteolytic mechanism to enhance epithelial cell migration. We propose that hemopexin homodimer formation is required for the full cell migratory function of proMMP-9.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
DOI：
10.1073/pnas.48.6.1014
发表时间：
1962-01-01
影响因子：
11.1
作者：
GROSS, J;LAPIERE, CM
通讯作者：
LAPIERE, CM
影响因子：
4.8
作者：
Cao, J;Drews, M;Zucker, S
通讯作者：
Zucker, S
影响因子：
4.8
作者：
Cao, JA;Rehemtulla, A;Zucker, S
通讯作者：
Zucker, S
影响因子：
5.6
作者：
Cha, HJ;Kopetzki, E;Brandstetter, H
通讯作者：
Brandstetter, H