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

作者：Leach Damien A; Need Eleanor F; Trotta Andrew P; Grubisha Melanie J; DeFranco Donald B; Buchanan Grant^*

来源：Molecular and Cellular Endocrinology, 2014, 384(1-2): 185-199.

DOI：10.1016/j.mce.2014.01.004

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

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.

• 出版日期2014-3-25