Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Sci. 2010 Apr;101(4):843-7. doi: 10.1111/j.1349-7006.2010.01498.x. Epub 2010 Jan 18.

Coordinate action of membrane-type matrix metalloproteinase-1 (MT1-MMP) and MMP-2 enhances pericellular proteolysis and invasion.

Author information

1
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. vhsato@kenroku.kanazawa-u.ac.jp

Abstract

Membrane-type matrix metalloproteinase-1 (MT1-MMP) mediates cleavage of not only MMP-2/gelatinase A for activation, but also a variety of substrates including type I collagen (reviewed in Cancer Sci 2005; 96: 212-7). MMP-2 activation involves tissue inhibitor of MMP (TIMP)-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. During invasive growth of tumor cells in type I collagen matrix, MT1-MMP initiates denaturation of collagen into gelatin, which is subsequently digested further by MMP-2 adjacent to MT1-MMP. Coordinate action of MT1-MMP and MMP-2 may facilitate pericellular proteolysis, and enhance not only tumor invasion/migration but also cell growth. Tetraspanins as binding proteins of MT1-MMP regulate MT1-MMP subcellular localization and compartmentalization, leading to efficient MMP-2 activation and proteolysis coupled with cellular function.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center