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Published on: March 27, 2020
ERG Activates the YAP1 Transcriptional Program and Induces the Development of Age-Related Prostate Tumors
Liem T Nguyen1, Maria S Tretiakova2, Mark R Silvis1
1Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Abstract:
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.
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