Androgen receptor–Src-family kinase complex (AR-SFK complex)

The Androgen receptor–Src-family kinase complex is a functional protein assembly that mediates the non-genomic signaling effects of androgens in various tissues, most notably in the prostate (Migliaccio et al., 2000, EMBO J). While the androgen receptor (AR) is primarily known as a ligand-activated transcription factor, it can also form a cytoplasmic or membrane-associated complex with members of the Src-family kinases (SFKs), particularly Src (Castoria et al., 2003, Cancer Res). This interaction typically involves the binding of the AR proline-rich domain to the SH3 domain of Src, which triggers the rapid activation of the Raf/MEK/ERK and PI3K/Akt pathways (Shafi et al., 2015, Front Biosci). In oncology, this complex is a major driver of prostate cancer progression and the development of castration-resistant prostate cancer (CRPC), as it promotes cell survival and motility even under low androgen conditions (Zhu et al., 2006, Mol Endocrinol). Therapeutic targeting of this complex often involves Src inhibitors like dasatinib or AR antagonists like enzalutamide, though research into specific disruptors of the AR-Src interface is ongoing to minimize off-target effects (PubMed, PMID: 25553444). The complex is also implicated in breast cancer, where it facilitates cross-talk between steroid receptors and growth factor signaling (UniProt, P10275). Monitoring biomarkers such as phosphorylated Src and AR levels is essential for evaluating the efficacy of treatments targeting this signaling axis (NIH, National Cancer Institute). Challenges in targeting this complex include the redundancy of Src-family kinases and the potential for compensatory signaling through other tyrosine kinases (StatPearls, Cancer Signaling).

Other names

AR-Src complexAndrogen receptor-Src kinase complexAR/Src complexAndrogen receptor-Src family kinase complex

Inhibition of the physical interaction between the androgen receptor and Src kinase or inhibition of the kinase activity within the complex to block non-genomic signaling.