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

Mengna Zhang1, Lingxian Zhang1, Ajun Geng2

  • 1Department 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.

Cell Reports
|September 14, 2022
PubMed

Insights

Cyclin-dependent kinase 14 (CDK14) is crucial for mammary gland development and triple-negative breast cancer (TNBC) progression. Inhibiting CDK14 may offer a new therapeutic strategy for TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The Wnt/β-catenin signaling pathway is vital for mammary gland development and cancer.
  • Targeting the Wnt pathway for breast cancer therapy remains challenging.
  • Cyclin-dependent kinase 14 (CDK14) is a component of the Wnt pathway.

Purpose of the Study:

  • To investigate the role of CDK14 in mammary development and breast cancer.
  • To evaluate CDK14 as a potential therapeutic target for triple-negative breast cancer (TNBC).

Main Methods:

  • CDK14 expression analysis in mammary tissues and TNBC.
  • CDK14 knockdown experiments in mammary basal cells and murine models.
  • Pharmacological inhibition of CDK14 using FMF-04-159-2.
  • Assessment of Wnt/β-catenin signaling activity.

Main Results:

  • CDK14 is expressed in the mammary basal layer and elevated in TNBC.
  • CDK14 knockdown impaired mammary basal cell colony formation and regeneration.
  • CDK14 inhibition reduced the progression and metastasis of TNBC in murine models.
  • CDK14 inhibition suppressed Wnt/β-catenin signaling.

Conclusions:

  • CDK14 plays a significant role in mammary development and TNBC progression.
  • CDK14 is a promising therapeutic target for TNBC.
  • Targeting CDK14 may be an effective strategy to attenuate Wnt/β-catenin signaling in TNBC.

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