TRIB3 promotes malignancy of head and neck squamous cell carcinoma via inhibiting ferroptosis

• DOI: 10.1038/s41419-024-06472-5
• Publication Date: 2024-03-01T06:03:16Z
• Authors: Li Chen; Wanzun Lin; Haojiong Zhang; Shikai Geng; Ziyu Le; Fangzhu Wan; Qingting Huang; Huaiyuan Chen; Xingyu Liu; Jiade J. Lu; Lin Kong
• Keywords: Repressor Proteins; 0303 health sciences; 03 medical and health sciences; QH573-671; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Humans; Ferroptosis; Cell Cycle Proteins; Protein Serine-Threonine Kinases; Cytology; Article

Abstract Tribbles pseudokinase 3 (TRIB3) has been identified recently as a novel oncogene in several cancers. Still, further extensive research is imperative to elucidate its function and the molecular mechanisms underlying involvement progression of head neck squamous cell carcinoma (HNSCC). In our study, we found that TRIB3 silencing significantly promoted death by inducing ferroptosis. The interaction with Transcription Factor 4 (TCF4) β-catenin created heterotrimeric complex, which directly interacts ALOXE3 promoter, detrimentally impacting activation. consequential partial neutralization ferroptosis induced deficiency observed through implementation knockdown. Furthermore, study demonstrated inhibitor hesperidin, targeting TRIB3, not only reduced malignancy but also ferroptosis, thereby suppressing tumor growth. Overall, findings unequivocally validate proposition precipitates iron mechanism, indicating strategic could emerge an innovative therapeutic strategy for HNSCC.