Coordinate action of membrane-type matrix metalloproteinase-1 (MT1-MMP) and MMP-2 enhances pericellular proteolysis and invasion.
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.
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. vhsato@kenroku.kanazawa-u.ac.jp
Hiroshi
H
Sato
Takahisa
T
Takino
D000818:Animals; D003094:Collagen / Q000378:metabolism / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D024042:Collagen Type I; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1