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

被引：14

作者：

Zhang, Mengna ^{[1
]}

Zhang, Lingxian ^{[1
]}

Geng, Ajun ^{[3
,4
]}

Li, Xiao ^{[1
]}

Zhou, Yu ^{[1
]}

Xu, Liming ^{[1
]}

Zeng, Yi Arial ^{[3
,4
]}

Li, Jinpeng ^{[2
]}

Cai, Cheguo ^{[1
]}

机构：

[1] Wuhan Univ, Zhongnan Hosp, Frontier Sci Ctr Immunol & Metab, Dept Thyroid & Breast Surg,Med Res Inst, Wuhan 430071, Peoples R China

[2] Wuhan Univ, Zhongnan Hosp, Dept Thyroid & Breast Surg, Wuhan, Peoples R China

[3] Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China

[4] Chinese Acad Sci, Univ Chinese Acad Sci, Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol,Shanghai Inst Biochem & C, Shanghai, Peoples R China

来源：

CELL REPORTS | 2022年 / 40卷 / 11期

基金：

中国国家自然科学基金;

关键词：

PROLIFERATION; EXPRESSION; DISEASE; MIGRATION; INVASION; GROWTH; LRP6;

D O I：

10.1016/j.celrep.2022.111331

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Wnt/beta-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/beta-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.

引用

页数：23

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