KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer

Abstract The new generation androgen receptor (AR) pathway inhibitor enzalutamide can prolong the survival of patients with metastatic prostate cancer. However, resistance to inevitably develops in these patients, and underlying mechanisms this are not fully defined. Here we demonstrate that kinesin family member 15 (KIF15) contributes by enhancing AR signaling cancer cells. KIF15 directly bound N-terminus AR/AR-V7 prevented proteins from degradation increasing protein association ubiquitin-specific protease 14 (USP14) AR/AR-V7. In turn, transcriptionally active stimulated expression. inhibitors alone or combination significantly suppressed enzalutamide-resistant cell growth xenograft progression. These findings highlight a key role enabling cells develop therapy rationalize as potential therapeutic target. Significance: how reciprocal activation between highlights cotargeting strategy for tumors.