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Cellular cholesterol regulates MT1 MMP dependent activation of MMP 2 via MEK‐1 in HT1080 fibrosarcoma cells
Author(s) -
Atkinson Susan J.,
English Jane L.,
Holway Nicholas,
Murphy Gillian
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.04.040
Subject(s) - ht1080 , matrix metalloproteinase , fibrosarcoma , protein kinase a , chemistry , secretion , microbiology and biotechnology , proteolysis , biochemistry , phosphorylation , mapk/erk pathway , kinase , cell , biology , enzyme , genetics
Unstimulated human fibrosarcoma cells (HT1080) constitutively secrete matrix metalloproteinase 2 (MMP 2) as a proenzyme requiring proteolytic cleavage by membrane type‐1 MMP (MT1 MMP) for activation. Physiological and pharmacological stimuli induce clustering of MT1 MMP/tissue inhibitor of MMP 2 “receptors”, promoting binding and activation of MMP 2. We now report that cholesterol depleted HT1080 cells accumulated MT1 MMP on the cell surface and activated MMP 2. A specific inhibitor of mitogen activated protein kinase kinase 1/2 inhibited both MMP 2 activation and extracellular signal‐related kinase phosphorylation induced by cholesterol depletion. Our data indicate that the cholesterol content of unstimulated cells is critical for secretion of MMP 2 as an inactive zymogen and control of pericellular proteolysis.