Hic-5 influences genomic and non-genomic actions of the androgen receptor in prostate myofibroblasts

Damien A. Leach, Eleanor F. Need, Andrew P. Trotta, Melanie J. Grubisha, Donald B. DeFranco, Grant Buchanan

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

There is extensive knowledge of androgen receptor (AR) signaling in cancer cells, but less regarding androgen action in stromal cells of the tumor microenvironment. We report here the genome-wide effects of a stromal cell specific molecular adapter and AR coregulator, hydrogen peroxide-inducible gene 5 (Hic-5/TGFB1I1), on AR function in prostate myofibroblasts. Following androgen stimulation, Hic-5 rapidly translocates to the nucleus, coincident with increased phosphorylation of focal adhesion kinase. As a coregulator, Hic-5 acted to amplify or inhibit regulation of approximately 50% of AR target genes, affected androgen regulation of growth, cell adhesion, motility and invasion. These data suggest Hic-5 as a transferable adaptor between focal adhesions and the nucleus of prostate myofibroblasts, where it acts a key mediator of the specificity and sensitivity of AR signaling. We propose a model in which Hic-5 coordinates AR signaling with adhesion and extracellular matrix contacts to regulate cell behavior in the tumor microenvironment.

Original languageEnglish
Pages (from-to)185-199
Number of pages15
JournalMolecular and Cellular Endocrinology
Volume384
Issue number1-2
DOIs
StatePublished - 25 Mar 2014
Externally publishedYes

Keywords

  • Androgen receptor
  • Fibroblasts
  • Focal adhesions
  • Microenvironment
  • Prostate cancer
  • Stroma

Fingerprint

Dive into the research topics of 'Hic-5 influences genomic and non-genomic actions of the androgen receptor in prostate myofibroblasts'. Together they form a unique fingerprint.

Cite this