Downregulation of HDGF Inhibits Tumorigenic Phenotypes of Hypopharyngeal Squamous Cell Carcinoma by Suppressing the AKT/mTOR/VEGF pathway

Hypopharyngeal squamous cell carcinoma (HSCC) poses a significant threat as one of the deadliest tumors within head and neck squamous cell carcinoma (HNSCC), often associated with regional metastasis. However, the precise mechanisms driving HSCC’s aggressive nature remain poorly understood. Hepatoma-derived growth factor (HDGF) exhibits aberrant expression across various malignancies, yet its specific role in HSCC remains unclear. In this study, we investigated the involvement and underlying molecular mechanisms of HDGF in HSCC. Our findings revealed high HDGF expression across a spectrum of tumors, including HNSCC. HDGF depletion significantly curtailed the proliferation, migration, and invasion of HSCC cells, notably FaDu cells. Furthermore, Western blot analysis unveiled that HDGF knockdown impeded the epithelial-mesenchymal transition (EMT) process in FaDu cells, evidenced by upregulated E-cadherin and downregulated N-cadherin, Snail, and Slug proteins. Additionally, HDGF knockdown led to a notable decrease in p-AKT, p-mTOR, and VEGFA expression in FaDu cells. In summary, our findings underscore HDGF’s pivotal role in HSCC progression. HDGF knockdown emerges as a potential strategy to inhibit FaDu cell proliferation, migration, invasion, and EMT, possibly through modulation of the AKT/mTOR/VEGF pathway. Thus, targeting HDGF holds promise as a therapeutic intervention for HSCC.