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

J Chemother. 2023 Nov;35(7):627-637. doi: 10.1080/1120009X.2022.2162221. Epub 2023 Jan 19.

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

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Transcription Factors / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins / drug effects
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins / metabolism
  • YAP-Signaling Proteins / drug effects
  • YAP-Signaling Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Metformin
  • Transcription Factors
  • YAP-Signaling Proteins
  • WWTR1 protein, human
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins