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

Cancer Cell. 2015 Jun 8;27(6):797-808. doi: 10.1016/j.ccell.2015.05.005.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Age Factors
  • Animals
  • Cell Cycle Proteins
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Phosphoproteins / antagonists & inhibitors
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Porphyrins / pharmacology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Random Allocation
  • Signal Transduction
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transcriptional Regulator ERG
  • Translocation, Genetic
  • Up-Regulation
  • Verteporfin
  • Xenograft Model Antitumor Assays
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • ERG protein, human
  • ERG protein, mouse
  • Oncogene Proteins
  • Phosphoproteins
  • Porphyrins
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Regulator ERG
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Yap1 protein, mouse
  • Verteporfin

Associated data

  • SRA/SRP041840