Abstract
Microplastics and nanoplastics are commonly found in our everyday environments. So far, microplastics and nanoplastics have been detected in various tissues and bodily fluids, including hair, sputum, digestive tissue, lungs, blood, placental and endometrial tissue. Although some studies indicate that microplastics and nanoplastics can promote tumor development, their impact on endometrial cancer (EC) remains unclear. In this study, we examined the effect of polystyrene nanoplastics (PS-NPs) on EC development and explored the underlying pathogenic mechanisms. We observed the uptake and accumulation of PS-NPs in HEC-1B cells and EC organoids. Through cell and organoid experiments as well as mouse models, we demonstrated that PS-NP exposure can accelerate EC progression in vitro and in vivo. Next, through transcriptomic sequencing and targeted metabolomic sequencing, We found that adenosine 5’-monophosphate-activated protein kinase (AMPK) can activate ACSS2 and promote its nuclear translocation. The nuclear entry of ACSS2 is associated with increased levels of H3K9 acetylation, which may be a potential mechanism through which it regulates PLA2G3 expression. PLA2G3 mRNA levels are upregulated, increasing the production of arachidonic acid (AA), and ultimately leads to the epithelial-mesenchymal transition (EMT) in EC cells. The relevant molecular markers in this study can provide new strategies for early warning and targeted intervention, reducing the potential impact of PS-NPs on EC.
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Data availability
All data generated or analysed during this study are included in this published article. The data used in this study include the publicly accessible TCGA endometrial cancer dataset, as well as newly generated sequencing data from this study—the related raw sequence data have been publicly deposited in the NCBI Sequence Read Archive under accession number PRJNA1418129 (access link: https://www.ncbi.nlm.nih.gov/sra/PRJNA1418129). The metabolomics data involved in this study have been deposited in the MetaboLights database, with the study identifier MTBLS13850 (access URL: https://www.ebi.ac.uk/metabolights/MTBLS13850).
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Funding
This work was supported by the National Natural Science Foundation of China [Grant No. 82272985 to Shuo Chen; Grant No.82203248 to Xin Liu]. Science and Technology Projects in Guangzhou [No.2024A03J0897; 2025A03J3761]; Natural Science Foundation of Guangdong Province, China [No. 2025A1515012402].
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XCH: Data curation, Formal analysis, Investigation, Writing – original draft. LX and JLW: Conceptualization, Writing – original draft, Investigation. JCC: Data curation. JY: Formal analysis. XL: Writing – review & editing, Funding acquisition. IL and JK: Writing – review & editing, YZ and SC: Supervision, Formal analysis, Writing – review & editing, Funding acquisition. All authors read and approved the final manuscript.
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The Ethics Committee of the third affiliated Hospital of Guangzhou Medical University approved the use of human tissue in this study [NO: 2020066]. Informed consent was obtained from all patients. Animal experiments were approved by the Guangdong Laboratory Animal Center (Foshan, Guangdong) [NO: B202411-6].
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Huang, X., Xu, L., Wang, J. et al. Polystyrene nanoparticles promote endometrial cancer development through the ACSS2-mediated reprogramming of arachidonic acid metabolism. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03071-5
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DOI: https://doi.org/10.1038/s41420-026-03071-5
