CDK11 Mediates Autophagy to Promote Breast Cancer Cell Proliferation and Migration by Regulating BCL‐2

Cyclin-dependent kinase 11 (CDK11), involved in various cellular processes including cell cycle regulation, apoptosis, and autophagy, is overexpressed in breast cancer and correlates with poor clinical outcomes. However, its exact mechanisms remain largely elusive. In the present study, we demonstrated that inhibiting CDK11 suppresses cell proliferation and migration and induces autophagy in breast cancer cells. The use of chloroquine (CQ) and ATG7 knockdown to block autophagy reversed the proliferation and migration inhibition caused by CDK11 reduction, indicating that induced autophagy suppresses breast cancer. Gene expression profiling revealed that CDK11 knockdown significantly downregulated the anti-apoptotic factor BCL-2. Further studies showed that overexpression of BCL-2 partially reversed the autophagy and the inhibition of proliferation and migration induced by CDK11 knockdown. Additionally, a mouse subcutaneous xenograft tumor model showed that BCL-2 overexpression partially rescued the tumor growth inhibition and reduction of LC3 expression induced by CDK11 knockdown. Taken together, these data reveal that inhibition of CDK11 induces autophagy and that CDK11 mediates autophagy to promote breast cancer cell proliferation and migration, with BCL-2 playing an important regulatory role in this process. These findings highlight that CDK11 may be a promising therapeutic target for the treatment of human breast cancer.