title: 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.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Liem T
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Tretiakova
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Silvis
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Lucas
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Klezovitch
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Ilsa
authors.initials: I
authors.lastname: Coleman
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Hamid
authors.initials: H
authors.lastname: Bolouri
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Vassily I
authors.initials: VI
authors.lastname: Kutyavin
authors.affiliation: Department of Urology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Colm
authors.initials: C
authors.lastname: Morrissey
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.affiliation: 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.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
authors.affiliation: 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.
authors.forename: Valeri
authors.initials: V
authors.lastname: Vasioukhin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D018797:Cell Cycle Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011166:Porphyrins / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D000071230:Transcriptional Regulator ERG; D014178:Translocation, Genetic; D015854:Up-Regulation; D000077362:Verteporfin; D023041:Xenograft Model Antitumor Assays; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C072312:ERG protein, human; C531115:ERG protein, mouse; D015513:Oncogene Proteins; D010750:Phosphoproteins; D011166:Porphyrins; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C486223:Yap1 protein, mouse; D000077362:Verteporfin