ERG is a critical regulator of Wnt/LEF1 signaling in prostate cancer.

ABSTRACT: Chromosomal translocations juxtaposing the androgen-responsive TMPRSS2 promoter with the ETS-family transcription factor ERG result in aberrant ERG upregulation in approximately 50% of prostate cancers. Studies to date have shown important roles of ERG in inducing oncogenic properties of prostate cancer. Its molecular mechanisms of action, however, are yet to be fully understood. Here, we report that ERG activates Wnt/LEF1 signaling cascade through multiple mechanisms. ERG bound to the promoters of various Wnt genes to directly increase ligand expression. Consequently, ERG overexpression increased active β-catenin level in the cells and enhanced TCF/LEF1 luciferase reporter activity, which could be partially blocked by WNT-3A inhibitor IWP-2. Most importantly, our data defined LEF1 as a di

SUBMITTER: Wu L 

PROVIDER: S-EPMC3790861 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature