Epigenetic control of the invasion-promoting MT1-MMP/MMP-2/TIMP-2 axis in cancer cells.

ABSTRACT: Membrane type-1 matrix metalloproteinase (MT1-MMP) is an activator of soluble MMP-2. The activity of both MMPs is regulated by their physiological inhibitor TIMP-2. An MT1-MMP/MMP-2/TIMP-2 axis plays a key role in the invasive behavior of many cell types. Despite its importance, epigenetic control of this pro-invasive axis is insufficiently studied, and, as a result, its modification in a rational and clinically beneficial manner is exceedingly difficult. Therefore, we performed an epigenetic analysis of the MT1-MMP, MMP-2, and TIMP-2 gene promoters in highly migratory glioblastoma cells and in low migratory breast carcinoma MCF-7 cells. We determined, for the first time, that the epigenetic control leading to the transcriptional silencing of both MMPs includes hypermethylation of the corr

SUBMITTER: Chernov AV 

PROVIDER: S-EPMC2676002 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature