Cellular cholesterol regulates MT1 MMP dependent activation of MMP 2 via MEK-1 in HT1080 fibrosarcoma cells.

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Atkinson SJ,English JL,Holway N,Murphy G

doi

10.1016/j.febslet.2004.04.040

keywords:

subject

Has Abstract

pub_date

2004-05-21 00:00:00

pages

65-70

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579304004430

journal_volume

566

pub_type

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