1,4-Dioxane Induces Epithelial-Mesenchymal Transition and Carcinogenesis in an Nrf2-Dependent Manner.

ABSTRACT: The carcinogenic potential of the environmental pollutant 1,4-dioxane (1,4-D) in humans is not yet fully understood or recognised. In this study, we provide evidence that 1,4-D acts as a carcinogen in human epithelial cells. Using the human bronchial epithelial cell line BEAS-2B, with or without CRISPR-Cas9-mediated Nrf2 knockout, we demonstrate that continuous exposure to environmentally relevant concentrations of 1.25-20 ppm 1,4-D over 2 months induces malignant transformation in an Nrf2-dependent manner. Transformed cells exhibit enhanced anchorage-independent growth in soft agar, increased migration and invasion, and tumorigenic potential in a xenograft mouse model. Integrated RNA sequencing and proteomics analyses reveal that 1,4-D robustly activates Nrf2 signalling, driving extracell

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12042698 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature