Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1950966 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2010 | 9 Pages |
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.