Document Detail

Membrane-type 1 matrix metalloproteinase modulates focal adhesion stability and cell migration.
MedLine Citation:
PMID:  16473349     Owner:  NLM     Status:  MEDLINE    
Membrane-type 1 matrix metalloproteinase (MT1-MMP) plays an important role in extracellular matrix-induced cell migration and the activation of extracellular signal-regulated kinase (ERK). We showed here that transfection of the MT1-MMP gene into HeLa cells promoted fibronectin-induced cell migration, which was accompanied by fibronectin degradation and reduction of stable focal adhesions, which function as anchors for actin-stress fibers. MT1-MMP expression attenuated integrin clustering that was induced by adhesion of cells to fibronectin. The attenuation of integrin clustering was abrogated by MT1-MMP inhibition with a synthetic MMP inhibitor, BB94. When cultured on fibronectin, HT1080 cells, which endogenously express MT1-MMP, showed so-called motile morphology with well-organized focal adhesion formation, well-oriented actin-stress fiber formation, and the lysis of fibronectin through trails of cell migration. Inhibition of endogenous MT1-MMP by BB94 treatment or expression of the MT1-MMP carboxyl-terminal domain, which negatively regulates MT1-MMP activity, resulted in the suppression of fibronectin lysis and cell migration. BB94 treatment promoted stable focal adhesion formation concomitant with enhanced phosphorylation of tyrosine 397 of focal adhesion kinase (FAK) and reduced ERK activation. These results suggest that lysis of the extracellular matrix by MT1-MMP promotes focal adhesion turnover and subsequent ERK activation, which in turn stimulates cell migration.
Takahisa Takino; Yumi Watanabe; Miyuki Matsui; Hisashi Miyamori; Tomoya Kudo; Motoharu Seiki; Hiroshi Sato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-13
Journal Detail:
Title:  Experimental cell research     Volume:  312     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-21     Completed Date:  2006-06-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1381-9     Citation Subset:  IM    
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
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MeSH Terms
Cell Adhesion / physiology
Cell Movement / drug effects,  physiology*
Enzyme Activation / drug effects,  physiology
Enzyme Inhibitors / pharmacology
Extracellular Matrix / drug effects,  genetics,  metabolism*
Extracellular Signal-Regulated MAP Kinases / drug effects,  metabolism*
Fibronectins / metabolism*,  pharmacology
Focal Adhesion Protein-Tyrosine Kinases / drug effects,  metabolism
Focal Adhesions / drug effects,  metabolism*
Hela Cells
Integrins / drug effects,  metabolism
Matrix Metalloproteinases / antagonists & inhibitors,  genetics,  metabolism*
Matrix Metalloproteinases, Membrane-Associated
Microfilaments / metabolism
Phosphorylation / drug effects
Protein Structure, Tertiary / physiology
Stress Fibers / metabolism
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Fibronectins; 0/Integrins; EC Adhesion Protein-Tyrosine Kinases; EC Signal-Regulated MAP Kinases; EC 3.4.24.-/Matrix Metalloproteinases; EC 3.4.24.-/Matrix Metalloproteinases, Membrane-Associated

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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