Microplastics accumulated in breast cancer patients lead to mitophagy via ANXA2-mediated endocytosis and IL-17 signaling pathway

Ziying Tian; Boni Ding; Yilin Guo; Jieyu Zhou; Su Jiang; Jiaxue Lu; Nan Li; Xiao Zhou; Wenling Zhang

doi:10.1016/j.envpol.2024.125321

Microplastics accumulated in breast cancer patients lead to mitophagy via ANXA2-mediated endocytosis and IL-17 signaling pathway

Environ Pollut. 2024 Nov 17;364(Pt 2):125321. doi: 10.1016/j.envpol.2024.125321. Online ahead of print.

Authors

Ziying Tian¹, Boni Ding², Yilin Guo³, Jieyu Zhou¹, Su Jiang¹, Jiaxue Lu¹, Nan Li¹, Xiao Zhou⁴, Wenling Zhang⁵

Affiliations

¹ Department of Medical Laboratory Science, The Third Xiangya Hospital, Central South University, Changsha, China; Department of Medical Laboratory Science, Xiangya School of Medicine, Central South University, Changsha, China.
² Breast and Thyroid Wards of the Third Xiangya Hospital, Central South University, Changsha, China.
³ Department of Blood Transfusion, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital, Zhengzhou, Henan, China.
⁴ Department of Medical Laboratory Science, The Third Xiangya Hospital, Central South University, Changsha, China; Department of Medical Laboratory Science, Xiangya School of Medicine, Central South University, Changsha, China. Electronic address: xiao_zhou@csu.edu.cn.
⁵ Department of Medical Laboratory Science, The Third Xiangya Hospital, Central South University, Changsha, China; Department of Medical Laboratory Science, Xiangya School of Medicine, Central South University, Changsha, China. Electronic address: zhangwenling@csu.edu.cn.

PMID: 39557355
DOI: 10.1016/j.envpol.2024.125321

Abstract

Breast cancer (BC) is the most common malignancy in women and the leading cause of cancer death. Microplastics (MPs) are plastic fragments with a diameter of less than 5 mm, easily ingested by organisms. Although MPs have been reported to enter the human body through diet, surgery, etc., whether MPs accumulate in BC and their effects have been largely unknown. Our study revealed a significant accumulation of MPs in BC patient samples. MPs pull-down experiments and mass spectrometry (MS) studies showed that MPs bound to annexin A2 (ANXA2) and were endocytosed into cells. This process resulted in mitochondrial damage and subsequent induction of mitophagy. Furthermore, after binding to ANXA2, MPs regulated mitophagy by inhibiting IL-17 exocytosis. These findings revealed the mechanism of toxic effects of MPs in patients with BC, clarified the molecular mechanism of ANXA2-IL-17 signaling pathway causing mitochondrial damage by MPs, and suggested the potential toxic effects and toxicological mechanisms of MPs.

Keywords: ANXA2; Breast cancer; IL-17 signaling pathway; Microplastics; Mitophagy.