Abstract

This study aims to uncover the role and mechanism of transforming growth factor α (TGFA) on the malignant progression of cervical cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to examine the expression levels of TGFA in cancer cells and tissues. Changes in cell viability, apoptosis, and malignant metastatic ability of cancer cells were detected using methylthiazolyldiphenyl-tetrazolium bromide (MTT), flow cytometry, and Transwell method respectively. Autophagy was evaluated via microtubule-associated proteins light chain 3 (LC3) and sequestosome 1 (p62) expression. A nude mouse xenograft model was used for in vivo validation. RNA pull-down assay was performed to explore the interaction between TGFA and desmoglein 2 (DSG2). These results indicated that TGFA expression was elevated in both cervical cancer tissues and cells. TGFA overexpression promoted cell proliferation, metastasis, and autophagy, whereas TGFA knockdown exerted the opposite effects and inhibited tumor growth. Mechanistically, TGFA bound to DSG2 and affected the downstream MYC oncogene (c-MYC)/ADAM metallopeptidase domain 17 (ADAM17) pathway. In conclusion, TGFA serves as an upstream regulator of the DSG2/c-MYC/ADAM17 axis, which is correlated with autophagy and malignant progression of cervical cancer.