Abstract
Background: SRY-related high-mobility-group box gene 4 (SOX4) is overexpressed in various cancers and has been studied as a therapeutic target in multiple malignancies. Therefore, this study aims to investigate the role of SOX4 in cancer progression and chemoradioresistance in head and neck squamous cell carcinoma (HNSCC). Methods: Utilizing in vitro silencing techniques and an orthotopic mouse xenograft model that simulates HNSCC biological characteristics, the effect of SOX4 modulation on cell proliferation, invasion, migration, and apoptosis was assessed. Results: The results showed that SOX4 knockdown led to significant inhibition of cell proliferation, reduced invasion and migration capabilities, and increased apoptosis in human HNSCC cells. Furthermore, SOX4 knockdown enhanced chemoradiosensitivity, as evidenced by increased apoptosis levels following treatment with cisplatin and irradiation. Conversely, SOX4 overexpression in an orthotopic mouse model of HNSCC significantly promotes tumor invasion, metastasis, and chemoresistance to cisplatin. Conclusions: These findings highlight the essential role of SOX4 in HNSCC progression and treatment resistance, suggesting SOX4 is a predictive biomarker and potential therapeutic target for improving treatment outcomes in patients with HNSCC.