The CXCL12/CXCR4 axis promotes ligand-independent activation of the androgen receptor

► The CXCL12/CXCR4 axis functionally activates the AR in the absence of androgen. ► CXCL12/CXCR4 promotes nuclear accumulation of the AR and SRC-1 co-regulator. ► CXCL12/CXCR4 stimulates AR-regulated gene transcription and cellular proliferation. ► CXCL12/CXCR4 activates AR and SRC-1 viaPI3K- and MAPK-mediated phosphorylation. ► CXCL12/CXCR4-mediated AR activation may provide a new therapeutic target.