NF‑κB‑driven LUZP1 promotes metastasis and chemoresistance in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) remains a highly aggressive malignancy with poor prognosis driven by metastasis and therapeutic resistance. Through comparative proteomic profiling of tumor specimens from patients with long‑ and short‑term survival, the present study identified leucine zipper protein 1 (LUZP1) as one of the most upregulated proteins in tumors from short‑term survivors. Functional assays revealed that LUZP1 knockdown impaired migration, invasion, invadopodia formation and epithelial‑mesenchymal transition, while enhancing sensitivity to docetaxel and cisplatin. Analysis of paired primary and metastatic tumors further confirmed elevated LUZP1 expression in metastatic sites. Mechanistically, NF‑κB inhibition markedly reduced LUZP1 expression, whereas stimulation with IL‑1β or TNF‑α induced its upregulation and rescued the migration defect caused by LUZP1 depletion, implicating NF‑κB as a key upstream regulator. Immunohistochemical analysis of clinical samples demonstrated that high LUZP1 expression was associated with shorter overall and progression‑free survival. Collectively, these findings identify LUZP1 as a novel NF‑κB‑regulated effector that promotes metastasis and chemoresistance and highlight its potential as a prognostic biomarker and therapeutic target in HNSCC.