title: Proteolytic and non-proteolytic roles of membrane type-1 matrix metalloproteinase in malignancy.
abstract: This manuscript provides an overview of the dynamic interactions which play an important role in regulating cancer cell functions. We describe and discuss, primarily, those interactions which involve membrane type-1 matrix metalloproteinase (MT1-MMP), its physiological inhibitor tissue inhibitor of metalloproteinases-2 (TIMP-2), furin-like proprotein convertases and the low density lipoprotein-related protein 1 (LRP1) signaling scavenger receptor. The interaction among these cellular proteins controls the efficiency of the activation of MT1-MMP and the unorthodox intracellular signaling which is generated by the catalytically inert complex of MT1-MMP with TIMP-2 and which plays a potentially important role in the migration of cancer cells. Our in-depth understanding of these cellular mechanisms may provide the key to solving the puzzling TIMP-2 paradox. This unsolved paradox arises from the fact that TIMP-2 is a powerful inhibitor of MMPs including MT1-MMP, but at the same time high levels of TIMP-2 positively correlate with an unfavorable prognosis in cancer patients. Solving the TIMP-2 paradox may lead to solving a similar PAI-1 paradox and produce a clearer understanding of the biochemical mechanisms which control the functionality of the urokinase-type plasminogen activator*urokinase receptor*plasminogen activator inhibitor type-1 (uPAR*uPA*PAI-1) system in cancer.
authors.affiliation: Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. strongin@burnham.org
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Strongin
mesh_terms: D000818:Animals; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D043484:Proprotein Convertases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D026503:Low Density Lipoprotein Receptor-Related Protein-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D043484:Proprotein Convertases; D053511:Matrix Metalloproteinase 14