Polyethylene terephthalate micro-/nanoplastics suppress SAT1-dependent ferroptosis in triple-negative breast cancer.

BACKGROUND: The potential association between micro-/nanoplastics and cancer has raised increasing concerns. However, research focusing specifically on breast cancer (BC), and particularly on triple-negative breast cancer (TNBC), remains limited, leading to a critical gap in current knowledge. This study seeks to explore potential correlative effects of micro-/nanoplastic exposure on TNBC progression. METHODS: We employed scanning electron microscopy, micro-Raman spectroscopy, and pyrolysis-gas chromatography-mass spectrometry to characterize micro-/nanoplastics in BC tissues. Moreover, spatial transcriptomics (ST) analysis was applied to characterize putative molecular changes associated with polyethylene terephthalate (PET) micro-/nanoplastic exposure and TNBC progression, followed by in vitro and in vivo assays to further investigate these changes. RESULTS: A variety of micro-/nanoplastics were detected in human BC tissues. Among them, based on the results of the ST analysis, PET might be related to the downregulation of spermine/spermidine N1-acetyltransferase 1 (SAT1) in TNBC tumor cells and the inhibition of ferroptosis. Moreover, in vitro and in vivo data showed that, following PET treatment, SAT1 expression and ferroptosis were significantly downregulated, whereas TNBC cell proliferation and xenograft growth were significantly upregulated. Additionally, in vitro experiments further suggested that PET micro-/nanoplastics could interact with BC cells via particle endocytosis or surface adsorption. CONCLUSIONS: This study suggests that SAT1-dependent ferroptosis may be a potential molecular pathway that links PET micro/nanoplastic exposure to TNBC progression. This finding provides novel insights into the possible toxicological association between micro-/nanoplastic exposure and TNBC progression.