Integrative Genomics Analysis Reveals Silencing of β-Adrenergic Signaling by Polycomb in Prostate Cancer

Jindan Yu, Qi Cao, Rohit Mehra, Bharathi Laxman, Jianjun Yu, Scott A. Tomlins, Chad J. Creighton, Saravana M. Dhanasekaran, Ronglai Shen, Guoan Chen, David S. Morris, Victor E. Marquez, Rajal B. Shah, Debashis Ghosh, Sooryanarayana Varambally, Arul M. Chinnaiyan*

*Corresponding author for this work

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

The Polycomb group (PcG) protein EZH2 possesses oncogenic properties for which the underlying mechanism is unclear. We integrated in vitro cell line, in vivo tumor profiling, and genome-wide location data to nominate key targets of EZH2. One of the candidates identified was ADRB2 (Adrenergic Receptor, Beta-2), a critical mediator of β-adrenergic signaling. EZH2 is recruited to the ADRB2 promoter and represses ADRB2 expression. ADRB2 inhibition confers cell invasion and transforms benign prostate epithelial cells, whereas ADRB2 overexpression counteracts EZH2-mediated oncogenesis. ADRB2 is underexpressed in metastatic prostate cancer, and clinically localized tumors that express lower levels of ADRB2 exhibit a poor prognosis. Taken together, we demonstrate the power of integrating multiple diverse genomic data to decipher targets of disease-related genes.

Original languageEnglish (US)
Pages (from-to)419-431
Number of pages13
JournalCancer Cell
Volume12
Issue number5
DOIs
StatePublished - Nov 13 2007

Keywords

  • CELLCYCLE
  • SYSBIO

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Yu, J., Cao, Q., Mehra, R., Laxman, B., Yu, J., Tomlins, S. A., Creighton, C. J., Dhanasekaran, S. M., Shen, R., Chen, G., Morris, D. S., Marquez, V. E., Shah, R. B., Ghosh, D., Varambally, S., & Chinnaiyan, A. M. (2007). Integrative Genomics Analysis Reveals Silencing of β-Adrenergic Signaling by Polycomb in Prostate Cancer. Cancer Cell, 12(5), 419-431. https://doi.org/10.1016/j.ccr.2007.10.016