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Extranuclear partners of androgen receptor: at the crossroads of proliferation, migration, and neuritogenesis
Author(s) -
Castoria Gabriella,
Auricchio Ferdinando,
Migliaccio Antimo
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601047r
Subject(s) - androgen receptor , receptor , microbiology and biotechnology , androgen , cell growth , biology , proto oncogene tyrosine protein kinase src , cancer research , prostate cancer , cell migration , medicine , endocrinology , signal transduction , cell , hormone , cancer , biochemistry , genetics
In this review, we focus on the role played by the protein partners of ligand‐activated extranuclear androgen receptor (AR) in the final effects of hormone action, such as proliferation, migration, and neuritogenesis. The choice of AR partner, at least in part, depends on cell type. Androgen‐activated receptor directly associates with cytoplasmic Src tyrosine kinase in epithelial cells, whereas in mesenchymal and neuronal cells, it prevalently interacts with filamin A. In the former, proliferation represents the final hormonal outcome, whereas in the latter, either migration or neuritogenesis, respectively, occurs. Furthermore, AR partner filamin A is replaced with Src when mesenchymal cells are stimulated with very low androgen concentrations. Consequently, the migratory effect is replaced by mitogenesis. Use of peptides that prevent receptor/partner assembly abolishes the effects that are dependent on their association and offers new therapeutic approaches to AR‐related diseases. Perturbation of migration is often associated with metastatic spreading in cancer. In turn, cell cycle aberration causes tumors to grow faster, whereas toxic signaling triggers neurodegenerative events in the CNS. Here, we provide examples of new tools that interfere in rapid androgen effects, including migration, proliferation, and neuronal differentiation, together with their potential therapeutic applications in AR‐dependent diseases—mainly prostate cancer and neurodegenerative disorders. —Castoria, G., Auricchio, F., Migliaccio, A. Extranuclear partners of androgen receptor: at the crossroads of proliferation, migration, and neuritogenesis. FASEB J . 31, 1289–1300 (2017) www.fasebj.org