We found that the AR immunofluorescence in the cells received the co-treatment of enzalutamide with IU1 or with USP14 siRNA was markedly less intense than in those received the single agent treatment; however, the nuclear and cytoplasmic distribution of AR staining was comparable among different treatment groups (Fig. 5b), indicating that the combined treatment exerts its synergistic effect on suppressing AR signaling mainly through reducing AR protein levels not suppressing AR nuclear translocation in breast cancer cells. The gene discussed is USP14; the disease is breast carcinoma.