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ERG Activates the YAP1 Transcriptional Program and Induces the Development of Age-Related Prostate Tumors.

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.

SUBMITTER: Nguyen LT

PROVIDER: S-EPMC4461839 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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ERG Activates the YAP1 Transcriptional Program and Induces the Development of Age-Related Prostate Tumors.

Nguyen Liem T LT Tretiakova Maria S MS Silvis Mark R MR Lucas Jared J Klezovitch Olga O Coleman Ilsa I Bolouri Hamid H Kutyavin Vassily I VI Morrissey Colm C True Lawrence D LD Nelson Peter S PS Vasioukhin Valeri V

Cancer cell 20150601 6

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, ...[more]

PMID: 26058078

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