In conclusion, the present results suggest that the ubiquitin E3 ligases FBW7 and MDM2 in the downstream of AR signaling play an important role in KCa1.1 protein degradation processes in breast cancer cells and provide novel insights into AR, VDR, and ubiquitin E3 kinase-targeted therapy for breast cancer with a poor prognosis. Here, FBXW7 is linked to breast carcinoma.