Emerging concepts in the regulation of membrane-type 1 matrix metalloproteinase activity.
Pericellular proteolysis mediated by membrane-type 1 matrix metalloproteinase (MT1-MMP) represents an essential component of the cellular machinery involved in the dissolution and penetration of ECM barriers by tumor cells. Although most studies on the proinvasive properties of MT1-MMP have focused on its unusually broad proteolytic activity towards several ECM components and cell surface receptors, recent evidence indicate that the cytoplasmic domain of the enzyme also actively participates in tumor cell invasion by regulating the cell surface localization of MT1-MMP as well as the activation of signal transduction cascades. The identification of the molecular events by which the intracellular domain of MT1-MMP links proteolysis of the surrounding matrix by the enzyme to modification of cell function may thus provide important new information on the mechanisms by which this enzyme controls the invasive behavior of neoplastic cells in vivo.
Gingras
Denis
D
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8.
Béliveau
Richard
R
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D053511:Matrix Metalloproteinase 14