EXTRA-NUCLEAR PARTNERS OF ANDROGEN RECEPTOR: AT THE CROSSROADS OF PROLIFERATION, MIGRATION AND NEURITOGENESIS.

This review focuses on the role played by protein partners of ligand-activated extra-nuclear AR in the final effects of hormone action, such as proliferation, migration and neuritogenesis. The choice of AR partners depends at least in part on cell type. The androgen-activated receptor directly associates with cytoplasmic Src tyrosine kinase in epithelial cells, while in mesenchymal and neuronal cells it prevalently interacts with FlnA. In the first case, proliferation represents the final hormonal outcome while in the latter either migration or neuritogenesis, respectively occur. Furthermore, the AR partner FlnA is replaced with Src when mesenchymal cells are stimulated with very low androgen concentrations. Consequently, the migratory effect is replaced by mitogenesis. The use of peptides preventing receptor/partner assembly abolishes the effects 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 tumours to grow faster, whereas toxic signalling triggers neurodegenerative events in central nervous system. Here, we provide examples of new tools interfering 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.