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

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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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Journal

Journal ID (iso-abbrev): Cancer Cell

Title: Cancer cell

ISSN (Electronic): 1878-3686

ISSN (Print): 1535-6108

Publication date (Electronic): Jun 8 2015

Volume: 27

Issue: 6

Affiliations

[1 ] Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

[2 ] Department of Pathology, University of Washington, Seattle, WA 98195, USA.

[3 ] Department of Urology, University of Washington, Seattle, WA 98195, USA.

[4 ] Department of Pathology, University of Washington, Seattle, WA 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.

[5 ] Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Urology, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Department of Pathology, University of Washington, Seattle, WA 98195, USA.

[6 ] Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Pathology, University of Washington, Seattle, WA 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA. Electronic address: vvasiouk@fhcrc.org.

Article

Publisher Item ID: S1535-6108(15)00181-6 Mid ID: NIHMS690705

DOI: 10.1016/j.ccell.2015.05.005

PMC ID: 4461839

PubMed ID: 26058078

SO-VID: b849892a-7d8b-4bca-80f5-630372a6ae8d

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