YAP/TAZ axis was involved in the effects of metformin on breast cancer

Abstract

Breast cancer is malignant tumours in women. A large amount of data analysis shows that Metformin has been shown to play a significance role in reducing the risk of breast cancer, but the mechanism remains unclear. The hippo signalling pathway can be involved in the formation, metastasis and recurrence of breast cancer. When YAP/TAZ is activated, cells can overcome contact inhibition and enter a state of uncontrolled proliferation. Therefore, YAP/TAZ is considered a potential therapeutic target for breast cancer. Eighty breast cancer patients, forty cases of triple-negative and forty cases of HER-2+, were included in this study. In vitro and in vivo experiments were used to confirm the YAP/TAZ axis was involved in the effects of metformin on breast cancer. EMT plays an important role in breast cancer, including chemoresistance and tumour metastasis. Our results confirmed that YAP could modulate the activity of EMT, which in turn altered tumour resistance. Therefore, MET can inhibit EMT by reducing the expression of YAP, and finally achieve the therapeutic effect of breast cancer. Our findings support metformin as a novel YAP inhibitor and potentially as a novel breast cancer drug.

Keywords:

• Metformin
• breast cancer
• YAP/TAZ activity
• hippo signalling pathway
• nuclear translocation
• novel drug
• epithelial–mesenchymal transition

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contribution

Jiayi Huang designed the study. Yu Xu and Hongke Cai performed the experiments. Yu Xu and Hongke Cai contributed equally to this work. Yuanfeng Xiong, Li Tang, Longjiang Li, Li Zhang, Yi Shen, Yongqiang Yang and Ling Lin gathered and analyzed the data, wrote the draft, and revised the manuscript. All authors read and approved the final manuscript.

Data availability statement

All authors make sure that all data and materials as well as software application or custom code support our published claims and comply with field standards.

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Chongqing Medical University. Informed consent was obtained from all individual participants included in the study.

Additional information

Funding

This study was funded by Chongqing Science and Technology Commission [grant no. cstc2018jscx-msybX0053] and Kuanren Talents Program of the Second Affiliate Hospital of Chongqing Medical University [grant no. kryc-gg-2112].