Blocking beta-catenin binding to the ZBP1 promoter represses ZBP1 expression, leading to increased proliferation and migration of metastatic breast-cancer cells.

ABSTRACT: ZBP1 (zipcode-binding protein 1, also known as IMP-1) is an mRNA regulator, functioning in mRNA localization, stability and translational control. ZBP1 is actively expressed during embryogenesis and tumorigenesis, but its expression is repressed in metastatic breast-cancer cell lines and tumors. In this article, we show that downregulation of ZBP1 expression results from its promoter methylation, an epigenetic process that remodels the chromatin structure and frequently represses gene activity. Demethylation of the ZBP1 promoter in metastatic cells reactivated ZBP1 expression, owing to restoration of the interaction of the ZBP1 promoter with beta-catenin. Loss of ZBP1 function not only increased growth ability of metastatic cells, but also promoted cell migration. We identified a number of

SUBMITTER: Gu W 

PROVIDER: S-EPMC2684840 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature