MMP14

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MMP14

A gene on chromosome 14q11-q12 that encodes matrix metalloproteinase 14, which specifically activates progelatinase A. It may be involved in actin cytoskeleton reorganisation by cleaving PTK7. Unlike other matrix metalloproteinases, which are secreted as inactive proproteins and activated when cleaved by extracellular proteinases, MMP14 is a transmembrane protein that is activated from its precursor by furin endopeptidase cleavage.

Molecular pathology
MMP14 may trigger invasion by tumour cells by activating progelatinase A on the surface of tumour cells.
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Moreover, MT1-MMP significantly downregulated during 1–4 weeks and soon recovered to normal levels.
TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa) B mediated induction of MT1-MMP.
Fibronectin upregulates gelatinase B (MMP-9) and induces coordinated expression of gelatinase A (MMP-2) and its activator MT1-MMP (MMP-14) by human T lymphocyte cell lines.
MMP-2 and MT1-MMP (MMP-14) are present in normal condition in latent or proforms in both human and experimental animals [7].
49) Tyrosine kinase substrate with 4 SH3 domains (Tks4), a Tks5-related protein, is important for the localization and stabilization of the transmembrane protease, MT1-MMP, in invadopodia.
Thus, MT1-MMP overexpression is correlated to that of MMP2 in carcinomas [79].
MT1-MMP is spatially and temporally regulated during MCF10A cell migration by peri-cellular proteolysis of the Ln-5 g2 chain.
Binding of active (57 kDa) membrane type 1-matrix metalloproteinase (MT1-MMP) to tissue inhibitor of metalloproteinase (TIMP)-2 regulates MT1-MMP processing and Pro-MMP-2 activation.
A MT1-MMP (MMP14) e a melhor caracterizada, e e responsavel pela ativacao da MMP-2 pela sua interacao com a TIMP-2, alem de atividades proteoliticas pericelulares (16).
Methylseleninic acid inhibits PMA-stimulated pro-MMP-2 activation mediated by MT1-MMP expression and further tumor invasion through suppression of NF-kappaB activation.
MMP-14, also called MT1-MMP, enhances local invasion and formation of metastases via pro-MMP-2 activation.
MT1-MMP, together with the tissue inhibitor of metalloproteinases 2, (111,112) is important in the activation of secreted proteases, such as MMP-2, (113) and suppression of MT1-MMP reduces overall matrix degradation activity (114) and invasion.