Role and Function of O-GlcNAcylation in Cancer
Overview
Authors
Affiliations
Cancer cells are able to reprogram their glucose metabolism and retain energy via glycolysis even under aerobic conditions. They activate the hexosamine biosynthetic pathway (HBP), and the complex interplay of O-linked N-acetylglucosaminylation (O-GlcNAcylation) via deprivation of nutrients or increase in cellular stress results in the proliferation, progression, and metastasis of cancer cells. Notably, cancer is one of the emerging diseases associated with O-GlcNAcylation. In this review, we summarize studies that delineate the role of O-GlcNAcylation in cancer, including its modulation in metastasis, function with receptor tyrosine kinases, and resistance to chemotherapeutic agents, such as cisplatin. In addition, we discuss the function of O-GlcNAcylation in eliciting immune responses associated with immune surveillance in the tumor microenvironment. O-GlcNAcylation is increasingly accepted as one of the key players involved in the activation and differentiation of T cells and macrophages. Finally, we discuss the prognostic role of O-GlcNAcylation and potential therapeutic agents such as O-linked β-N-acetylglucosamine-transferase inhibitors, which may help overcome the resistance mechanism associated with the reprogramming of glucose metabolism.
Crosstalk between O-GlcNAcylation and phosphorylation in metabolism: regulation and mechanism.
Zhao Q, Zhou S, Lou W, Qian H, Xu Z Cell Death Differ. 2025; .
PMID: 40045035 DOI: 10.1038/s41418-025-01473-z.
DC. Regulates Vascular Smooth Muscle Cell Proliferation by Modulating -GlcNAc and MOF Expression.
Na H, Kim J, Kim Y, Lee S, Sung M Prev Nutr Food Sci. 2025; 29(4):430-440.
PMID: 39759825 PMC: 11699568. DOI: 10.3746/pnf.2024.29.4.430.
Zhang Y, Qiao Z, He M, Xia J Immunol Res. 2024; 73(1):7.
PMID: 39666251 DOI: 10.1007/s12026-024-09567-5.
Wang M, Zhu W, Guo Y, Zeng H, Liu J, Liu J Metab Brain Dis. 2024; 40(1):16.
PMID: 39560836 DOI: 10.1007/s11011-024-01420-w.
Glut3 promotes cellular O-GlcNAcylation as a distinctive tumor-supportive feature in Treg cells.
Sharma A, Sharma G, Gao Z, Li K, Li M, Wu M Cell Mol Immunol. 2024; 21(12):1474-1490.
PMID: 39468304 PMC: 11606946. DOI: 10.1038/s41423-024-01229-8.