Document Detail

Up-regulation of vascular endothelial growth factor-A by active membrane-type 1 matrix metalloproteinase through activation of Src-tyrosine kinases.
MedLine Citation:
PMID:  14729679     Owner:  NLM     Status:  MEDLINE    
Membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF) are two key molecules involved in pericellular proteolysis and cell proliferation during tumor growth and angiogenesis. Our previous data showed that MT1-MMP overexpression in human breast carcinoma MCF7 cells induced an up-regulation of VEGF expression. This effect was associated in vivo with accelerated tumor growth and angiogenesis. We now provide evidence that MT1-MMP overexpression specifically affected VEGF-A production and failed to influence that of other VEGF family members (VEGF, B, C, D, or PlGF) or their receptors. The up-regulation of VEGF-A by MT1-MMP was related to an increased transcriptional activation rather than to a modification of mRNA stability. It was blocked by synthetic MMP inhibitors, TIMP2, but not TIMP-1 and abolished by a partial deletion of the catalytic domain or the cytoplasmic tail of MT1-MMP. Analysis of the signal transduction mechanisms demonstrated that MT1-MMP acts through a signaling pathway involving Src tyrosine kinases. Thus, our results provide new insight into the mechanisms of action of MT1-MMP during angiogenesis and suggest that the full enzymatic activity of MT1-MMP is required for a specific up-regulation of VEGF-A through an activation of Src tyrosine kinase pathways.
Nor Eddine Sounni; Christian Roghi; Vincent Chabottaux; Mathias Janssen; Carine Munaut; Erik Maquoi; Beatriz G Galvez; Christine Gilles; Francis Frankenne; Gillian Murphy; Jean-Michel Foidart; Agnès Noel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-01-16
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-29     Completed Date:  2004-05-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13564-74     Citation Subset:  IM    
Laboratory of Tumor and Development Biology University of Liège, Sart Tilman, 4000 Sart-Tilman, B-4000 Liège, Belgium.
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MeSH Terms
Amino Acid Sequence
Catalytic Domain
Cell Line, Tumor
Gene Expression
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases / chemistry,  metabolism*
Neovascularization, Physiologic / physiology*
Protein Structure, Tertiary
RNA, Messenger / metabolism
Vascular Endothelial Growth Factor A / genetics*
src-Family Kinases / metabolism*
Reg. No./Substance:
0/RNA, Messenger; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; EC Kinases; EC 3.4.24.-/Matrix Metalloproteinases, Membrane-Associated; EC 3.4.24.-/Metalloendopeptidases

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