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<p>O-GlcNAcylation is a dynamic post-translational modification of serine/threonine residues in proteins that modulates cellular activities by influencing the function of protein substrates, including their cellular localization, stability, and protein–protein interactions. The hexosamine biosynthesis pathway (HBP) utilizes various metabolites to synthesize uridine diphosphate N-acetylglucosamine, which serves as the substrate for O-GlcNAcylation. Metabolic reprogramming of tumors modulates HBP flux, thereby influencing O-GlcNAcylation levels. O-GlcNAcylation plays a pivotal role in regulating immune signaling pathways and their targets. Consequently, O-GlcNAcylation may act as a central node linking metabolic reprogramming and immune evasion. In this review, we summarize the current progress in understanding the role of O-GlcNAcylation in immunometabolism and explore how O-GlcNAcylation serves as a metabolic–immune translator that regulates tumor progression and therapeutic responses. Furthermore, we discuss the potential of O-GlcNAcylation as a therapeutic target, providing a promising new approach for cancer treatment.</p>

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O-GlcNAcylation: the metabolic-immune translator in tumor evolution and treatment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月20日

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  • Jinwen Zhao,
  • Jincai Lv,
  • Huanhuan Wang,
  • Zhuangzhuang Zheng,
  • Ying Xin,
  • Xin Jiang

摘要

O-GlcNAcylation is a dynamic post-translational modification of serine/threonine residues in proteins that modulates cellular activities by influencing the function of protein substrates, including their cellular localization, stability, and protein–protein interactions. The hexosamine biosynthesis pathway (HBP) utilizes various metabolites to synthesize uridine diphosphate N-acetylglucosamine, which serves as the substrate for O-GlcNAcylation. Metabolic reprogramming of tumors modulates HBP flux, thereby influencing O-GlcNAcylation levels. O-GlcNAcylation plays a pivotal role in regulating immune signaling pathways and their targets. Consequently, O-GlcNAcylation may act as a central node linking metabolic reprogramming and immune evasion. In this review, we summarize the current progress in understanding the role of O-GlcNAcylation in immunometabolism and explore how O-GlcNAcylation serves as a metabolic–immune translator that regulates tumor progression and therapeutic responses. Furthermore, we discuss the potential of O-GlcNAcylation as a therapeutic target, providing a promising new approach for cancer treatment.