Figure 2.

Reciprocal activation of Src and the androgen receptor through direct physical interaction. (A) Src activation is induced by several extracellular signals such as neuromediators produced by neighboring tumor cells with neuroendocrine differentiation, growth factors produced by neighboring tumor or stromal cells. Through direct physical interaction with the AR, Src is able to phosphorylate the AR and thereby induce ligand-independent AR activation (one of the key mechanisms of castration-resistant prostate cancer). Molecular mechanisms include increased AR translocation to the nucleus, decreased proteasomal degradation, decreased interaction with co-repressors (CoR), and/or increased acetylation. The result is the activation of AR-dependent gene expression programs. (B) Conversely, upon ligand binding and direct physical interaction with Src, the AR is able to induce Src activation, which is one of the cellular events associated with oncogenic transformation.