Luteolin suppresses epithelial-mesenchymal transition and migration of triple-negative breast cancer cells by inhibiting YAP/TAZ activity

被引：65

作者：

Cao, Dai ^{[1
]}

Zhu, Guo-Yuan ^{[2
]}

Lu, Yan ^{[3
]}

Yang, Aiping ^{[3
]}

Chen, Die ^{[3
]}

Huang, Hui-Jie ^{[3
]}

Peng, Shu-Xian ^{[1
]}

Chen, Li-Wen ^{[4
]}

Li, Ying-Wei ^{[1
]}

机构：

[1] Guangzhou Univ Chinese Med, Res Ctr Integrat Med, Sch Basic Med Sci, Guangzhou, Guangdong, Peoples R China

[2] Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Macau, Peoples R China

[3] Guangzhou Univ Chinese Med, Sch Basic Med Sci, Guangzhou, Guangdong, Peoples R China

[4] Guangzhou Univ Chinese Med, Artemisinin Res Ctr, Guangzhou, Guangdong, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2020年 / 129卷

基金：

中国国家自然科学基金;

关键词：

Luteolin; Triple-negative breast cancer; YAP/TAZ activity; Epithelial to mesenchymal transition; TEAD; YAP; METASTASIS; EMT;

D O I：

10.1016/j.biopha.2020.110462

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Triple-negative breast cancer (TNBC) is a highly lethal subtype of breast cancer associated with early relapse and metastasis. Epithelial to mesenchymal transition (EMT) plays pivotal roles in the progression of TNBC, including inducing cancer stem cell (CSC) properties, chemoresistance, tumor metastasis, and recurrence. Abnormally activated YAP/TAZ induces EMT in TNBC, making it a promising target for drug development. Our goal is to identify potential YAP/TAZ inhibitors from naturally derivative molecules and further study its effects on inhibiting EMT and metastasis of TNBC. In the current study, we demonstrate that luteolin significantly inhibits YAP/TAZ activity by promoting YAP/TAZ degradation in TNBC cells. Luteolin treatment leads to a decrease of mesenchymal markers and an increase of epithelial markers in both TNBC cells and TAZ-induced mesenchymal cells. Consistently, luteolin treatment inhibits cell migration in TNBC cells. Additionally, luteolin inhibits tumor growth in mice xenografted with TNBC cells. Collectively, our results support luteolin as a novel YAP/TAZ inhibitor for development as a new agent for the treatment of TNBC.

引用

页数：9

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