Apigenin suppresses the stem cell-like properties of triple-negative breast cancer cells by inhibiting YAP/TAZ activity

Triple-negative breast cancer (TNBC) remains a clinical challenge because of the absence of effective therapeutic targets. In TNBC, overexpression of YAP and TAZ correlates with bioactivities of cancer stem cells (CSCs), high histological grade, resistance to chemotherapy, and metastasis. Thus, YAP/...

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Published inCell death discovery Vol. 4; no. 1; pp. 105 - 9
Main Authors Li, Ying-Wei, Xu, Jian, Zhu, Guo-Yuan, Huang, Zhu-Juan, Lu, Yan, Li, Xian-Qian, Wang, Neng, Zhang, Feng-Xue
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 20.11.2018
Springer Nature B.V
Subjects
631/67
631/92
Apoptosis
Biochemistry
Biomedical and Life Sciences
Breast cancer
Cell Biology
Cell Cycle Analysis
Cell migration
Cell proliferation
Chemotherapy
Connective tissue growth factor
CYR61 protein
Life Sciences
Metastases
Stem Cells
Therapeutic applications
Yes-associated protein
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Summary:Triple-negative breast cancer (TNBC) remains a clinical challenge because of the absence of effective therapeutic targets. In TNBC, overexpression of YAP and TAZ correlates with bioactivities of cancer stem cells (CSCs), high histological grade, resistance to chemotherapy, and metastasis. Thus, YAP/TAZ may serve as potential therapeutic targets in TNBC. To identify YAP/TAZ inhibitors, in previous experiments, we screened a library of natural compounds by using YAP/TAZ luciferase reporter assay and identified apigenin as a potential inhibitor. In this study, we demonstrated that apigenin significantly suppressed the proliferation and migration of TNBC cells. Furthermore, we demonstrated that apigenin inhibited stemness features of TNBC cells in both in vitro and in vivo assays. Our mechanism study demonstrated that apigenin decreased YAP/TAZ activity and the expression of target genes, such as CTGF and CYR61, in TNBC cells. We also showed that apigenin disrupted the YAP/TAZ-TEADs protein–protein interaction and decreased expression of TAZ sensitized TNBC cells to apigenin treatment. Collectively, our studies suggest that apigenin is a promising therapeutic agent for the treatment of TNBC patients with high YAP/TAZ activity.
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ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-018-0124-8