Caveolin-1 inhibits membrane-type 1 matrix metalloproteinase activity.
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent proteinase found in cholesterol-rich lipid rafts on the plasma membrane. MT1-MMP hydrolyzes extracellular matrix (ECM) proteins, activates pro-matrix metalloproteinase-2 (proMMP-2) and plays an important role in ECM remodeling, cancer cell migration and metastasis. The role of caveolin-1, an integral protein of caveolae, in the activation of MT1-MMP remains largely unknown. Here, we show that the expression of caveolin-1 attenuates the activation of proMMP-2, reduces proteolytic cleavage of ECM and inhibits cell migration. We utilized the cytoplasmic tail domain deletion (DeltaCT) or the E240A mutant of MT1-MMP. Co-expression of caveolin-1 with the wild-type or the DeltaCT MT1-MMP decreased the proMMP-2 activation and inhibited collagen degradation and cell migration. Caveolin-1 had no effect on the catalytically inert E240A MT1-MMP. Our findings suggest that caveolin-1 is essential in the down-regulation of MT1-MMP activity by promoting internalization from the cell surface.
Kim
Hye-Nan
HN
Department of Biotechnology, Hannam University, Daejeon 305-811, Korea.
Chung
Hye-Shin
HS
D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002522:Chlorocebus aethiops; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection
C495540:CAV1 protein, human; D051242:Caveolin 1; D017931:DNA Primers; D004792:Enzyme Precursors; D061965:Matrix Metalloproteinase Inhibitors; D011994:Recombinant Proteins; D003094:Collagen; D018093:Gelatinases; C069860:progelatinase; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14