The role of transforming growth factor alpha in mediating the malignant transformation of human lung epithelial cells induced by single-walled carbon nanotubes and its role in the progression of non-small cell lung cancer

Single-walled carbon nanotubes (SWCNT), as emerging nanomaterials, possess unclear potential carcinogenic mechanisms. This study established a model of malignant transformation using human lung epithelial cells chronically treated with SWCNT, and applied integrated multi-omics analysis to identify key regulatory factors. Chronic exposure to SWCNT promoted cellular growth, motility, invasive potential, and oncogenic capacity, and activated the PI3K/AKT pathway, facilitating malignant transformation of the cells. Among the upregulated genes, Transforming Growth Factor Alpha (TGFA) was identified as a core regulatory factor. It was significantly overexpressed in malignant transformed cells, lung cancer cells of the non-small cell type (NSCLC), and patient-derived cancer tissues. Further investigation revealed that high TGFA expression was closely associated with poor prognosis and an immune-suppressive microenvironment in patients with lung adenocarcinoma and squamous cell carcinoma. Knockdown of TGFA inhibited the epithelial-mesenchymal transition (EMT) process and the activation of the PI3K/AKT signaling pathway, significantly weakening the malignant phenotype of the cells. Additionally, drug sensitivity analysis suggested that TGFA might be involved in regulating drug responses. In conclusion, TGFA functions as an essential regulator in the carcinogenic effects of SWCNT and holds potential diagnostic, prognostic, and therapeutic value for NSCLC.