Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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YPEL3 expression induces cellular senescence via the Hippo signaling pathway in human breast cancer cells

  • Yeonju Kwon (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) ;
  • Hyein Lee (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) ;
  • Hyemin Park (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) ;
  • Boyoung Lee (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) ;
  • Tae‑Uk Kwon (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) ;
  • Yeo‑Jung Kwon (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) ;
  • Young‑Jin Chun (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University)
  • Received : 2023.06.28
  • Accepted : 2023.08.14
  • Published : 2023.10.15
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Abstract

The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis. In this study, we found that YAP1 inhibits the expression of YPEL3 expression in breast cancer cells. Furthermore, a decrease in lamin B1, a marker protein of cellular senescence, coupled with the activation of senescence-associated β-galactosidase indicated that upregulating YPEL3 levels through YAP1 downregulation can induce cellular senescence. Additionally, elevated YPEL3 levels resulted in higher levels of oxygen consumption rate in mitochondria, thus promoting apoptosis. This suggests that YPEL3 plays a crucial role in regulating oxidative stress and cell apoptosis in breast cancer cells. Therefore, the interaction between YAP1 and YPEL3 represents a novel mechanism of cellular senescence mediated by the Hippo signaling pathway. Collectively, our fndings suggest that the Hippo signaling pathway plays an important role in regulating cellular senescence, which could have implications for the development of new therapeutic strategies for diseases such as cancer.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP) (Grant no. 2021R1A2C201239513, 2022R1A5A600076012) and the Chung-Ang University Graduate Research Scholarship in 2021. The funding agency had no role in the study design, data collection or analysis, the decision to publish, or the preparation of the manuscript.

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