[PDF][PDF] ERG activates the YAP1 transcriptional program and induces the development of age-related prostate tumors

LT Nguyen, MS Tretiakova, MR Silvis, J Lucas… - Cancer cell, 2015 - cell.com
LT Nguyen, MS Tretiakova, MR Silvis, J Lucas, O Klezovitch, I Coleman, H Bolouri
Cancer cell, 2015cell.com
The significance of ERG in human prostate cancer is unclear because mouse prostate is
resistant to ERG-mediated transformation. We determined that ERG activates the
transcriptional program regulated by YAP1 of the Hippo signaling pathway and found that
prostate-specific activation of either ERG or YAP1 in mice induces similar transcriptional
changes and results in age-related prostate tumors. ERG binds to chromatin regions
occupied by TEAD/YAP1 and transactivates Hippo target genes. In addition, in human …
Summary
The significance of ERG in human prostate cancer is unclear because mouse prostate is resistant to ERG-mediated transformation. We determined that ERG activates the transcriptional program regulated by YAP1 of the Hippo signaling pathway and found that prostate-specific activation of either ERG or YAP1 in mice induces similar transcriptional changes and results in age-related prostate tumors. ERG binds to chromatin regions occupied by TEAD/YAP1 and transactivates Hippo target genes. In addition, in human luminal-type prostate cancer cells, ERG binds to the promoter of YAP1 and is necessary for YAP1 expression. These results provide direct genetic evidence of a causal role for ERG in prostate cancer and reveal a connection between ERG and the Hippo signaling pathway.
cell.com