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

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.