CDK14 inhibition reduces mammary stem cell activity and suppresses triple negative breast cancer progression

The Wnt/β-catenin signaling pathway plays an important role in regulating mammary organogenesis and oncogenesis. However, therapeutic methods targeting the Wnt pathway against breast cancer have been limited. To address this challenge, we investigate the function of cyclin-dependent kinase 14 (CDK14), a member of the Wnt signaling pathway, in mammary development and breast cancer progression. We show that CDK14 is expressed in the mammary basal layer and elevated in triple negative breast cancer (TNBC). CDK14 knockdown reduces the colony-formation ability and regeneration capacity of mammary basal cells and inhibits the progression of murine MMTV-Wnt-1 basal-like mammary tumor. CDK14 knockdown or pharmacological inhibition by FMF-04-159-2 suppresses the progression and metastasis of TNBC. Mechanistically, CDK14 inhibition inhibits mammary regeneration and TNBC progression by attenuating Wnt/β-catenin signaling. These findings highlight the significance of CDK14 in mammary development and TNBC progression, shedding light on CDK14 as a promising therapeutic target for TNBC. [Display omitted] •CDK14 regulates the activities of MaSCs and BCSCs via Wnt/β-catenin signaling•CDK14 inhibition suppresses the progression and metastasis of TNBC•CDK14 inhibitor FMF-04-159-2 shows promising potential for the treatment of TNBC Zhang et al. show that CDK14 facilitates Wnt signaling to regulate the activity of mammary stem cells and breast cancer stem cells and that pharmacological inhibition of CDK14 by FMF-04-159-2 suppresses the progression and metastasis of triple negative breast cancer.