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

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

  • Cell Rep. 2022 Sep 13;40(11):111331. doi: 10.1016/j.celrep.2022.111331.
Mengna Zhang 1,  Lingxian Zhang 1,  Ajun Geng 2,  Xiao Li 1,  Yu Zhou 1,  Liming Xu 1,  Yi Arial Zeng 3,  Jinpeng Li 4,  Cheguo Cai 5
Affiliations

Affiliations

  • 1 Department of Thyroid and Breast Surgery, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • 2 School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 3 School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. Electronic address: yzeng@sibcb.ac.cn.
  • 4 Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China. Electronic address: lijinpeng3202@126.com.
  • 5 Department of Thyroid and Breast Surgery, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China. Electronic address: cheguo_cai@whu.edu.cn.
PMID: 36103813 DOI: 10.1016/j.celrep.2022.111331
Abstract

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.

Keywords

CDK14; CP: Cancer; Wnt/β-catenin signal; mammary stem cell; triple negative breast cancer.

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