Hic-5 influences genomic and non-genomic actions of the androgen receptor in prostate myofibroblasts.
Mol Cell Endocrinol, 2014/3/25;384(1-2):185-99.
Leach DA[1], Need EF[1], Trotta AP[1], Grubisha MJ[2], DeFranco DB[2], Buchanan G[3]
Affiliations
PMID: 24440747
Impact factor: 4.369
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.
Keywords: Androgen receptor; Fibroblasts; Focal adhesions; Microenvironment; Prostate cancer; Stroma
MeSH terms
Androgens; Cell Adhesion; Cell Line, Transformed; Cell Movement; Cell Nucleus; Focal Adhesion Protein-Tyrosine Kinases; Focal Adhesions; Gene Expression Regulation; Humans; Intracellular Signaling Peptides and Proteins; LIM Domain Proteins; Male; Molecular Sequence Annotation; Myofibroblasts; Phosphorylation; Prostate; Protein Transport; Receptors, Androgen; Signal Transduction; Stromal Cells; Testosterone; Tumor Microenvironment
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