Androgen receptor and Tyrosine-protein kinase Src interaction

The **Androgen receptor and Tyrosine-protein kinase Src interaction** is a critical node in oncogenic signaling in prostate cancer. AR is a nuclear hormone receptor that, when activated by androgens, translocates to the nucleus and modulates gene transcription controlling cell proliferation and survival. SRC is the prototypic member of the Src family non-receptor tyrosine kinases, associated with numerous cellular processes including migration, invasion, and survival. AR physically interacts with SRC, particularly through AR's proline-rich domain and SRC’s SH3 domain[1][2][4]. This interaction results in mutual activation: SRC phosphorylates AR (notably at Tyr534), promoting AR nuclear translocation and transcriptional activity, even under low androgens (ligand-independent activation)[1][2][6][7]. Reciprocally, AR can modulate SRC signaling via transcriptional and possibly non-genomic mechanisms. This crosstalk is especially relevant in castration-resistant prostate cancer, where simultaneous upregulation or co-activation of AR and SRC drives tumor proliferation, survival, migration, and therapy resistance[2][4][6]. Therapeutically, both AR and SRC are independently targeted, and dual-blockade or inhibition of this interaction is an area of preclinical and translational interest. The AR–SRC axis also intersects with other signaling pathways, including EGFR and MAPK, increasing oncogenic complexity[3][7].

Other names

AR–Src complexAndrogen receptor–Src interactionAR/Src complexAR–c-Src interaction

AR antagonists inhibit androgen binding, block AR–SRC interaction, or reduce AR nuclear translocation, suppressing AR-dependent proliferation\nSRC inhibitors block SRC kinase activity, thereby preventing AR phosphorylation and downstream signaling, including ligand-independent AR activation\nSome kinase inhibitors disrupt the physical AR–SRC interaction, blunting oncogenic synergism