Abstract

Background Head and neck squamous cell carcinoma (HNSCC) remains an aggressive malignancy with a poor prognosis, necessitating the identification of novel therapeutic targets and molecular mechanisms. Ferroptosis, an iron-dependent form of programmed cell death, is implicated in tumor progression. COL10A1 is dysregulated in various cancers, but its role and mechanism in HNSCC are unclear. This study aimed to investigate the expression, clinical significance, and functional mechanism of COL10A1 in HNSCC, focusing on its interaction with ANXA5 and regulation of ferroptosis. Methods COL10A1 expression was measured in HNSCC tissues and cell lines using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot, and its expression in paraffin-embedded HNSCC tissues was detected by immunohistochemistry. The protein ANXA5, which interacts with COL10A1, was screened, and the effects of COL10A1 and ANXA5 on HNSCC cells were analyzed. GPX4 expression was detected by immunofluorescence, RT-qPCR and Western blot. Reactive oxygen species in HNSCC cells were detected by flow cytometry, and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) was measured by enzyme-linked immunoassay. Results COL10A1 expression was increased in HNSCC cells and cancer tissues. Interference with COL10A1 expression inhibited HNSCC cell proliferation, migration, and invasion and enhanced apoptosis. ANXA5, found to be increased in HNSCC, interacts with COL10A1. Interference with COL10A1 or ANXA5 expression suppressed malignant progression and promoted ferroptosis of HNSCC cells. Conclusions COL10A1 is expressed abnormally in HNSCC and modulates cell proliferation, migration, invasion, apoptosis, and ferroptosis through its interaction with ANXA5.