Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors.

Metabolic reprogramming is a hallmark of cancer. Tumor cells adapt to their environment by modulating glucose, lipid, and amino acid metabolism to supply raw materials for rapid growth and enhance treatment resistance. Among these, glucose metabolic reprogramming is particularly critical. In head and neck tumor cells, glycolysis-derived intermediate metabolites provide biosynthetic precursors and energy necessary for growth, sustaining proliferation and invasion. Additionally, these metabolites can remodel the tumor microenvironment, modulate signaling pathways, and alter tumor phenotypes, further promoting chemoresistance and radioresistance. Protein homeostasis (proteostasis) refers to the dynamic balance of cellular processes involving protein synthesis, folding, modification, transport, and degradation, which is essential for maintaining normal physiological functions. This review aims to explore how proteostasis-regulated degradation pathways-specifically the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway-modulate glycolysis in head and neck tumors, thereby influencing tumor proliferation and invasion. These insights may provide a theoretical foundation for overcoming treatment resistance and improving prognosis, while also opening new avenues for future therapeutic research in head and neck oncology.