O-GlcNAcylation in cancer development and immunotherapy

O-linked β-D-N-acetylglucosamine (O-GlcNAc), as a posttranslational modification (PTM), is a reversible reaction that attaches β-N-GlcNAc to Ser/Thr residues on specific proteins by O-GlcNAc transferase (OGT). O-GlcNAcase (OGA) removes the O-GlcNAc from O-GlcNAcylated proteins. O-GlcNAcylation regulates numerous cellular processes, including signal transduction, the cell cycle, metabolism, and energy homeostasis. Dysregulation of O-GlcNAcylation contributes to the development of various diseases, including cancers. Accumulating evidence has revealed that higher expression levels of OGT and hyper-O-GlcNAcylation are detected in many cancer types and governs glucose metabolism, proliferation, metastasis, invasion, angiogenesis, migration and drug resistance. In this review, we describe the biological functions and molecular mechanisms of OGT- or O-GlcNAcylation-mediated tumorigenesis. Moreover, we discuss the potential role of O-GlcNAcylation in tumor immunotherapy. Furthermore, we highlight that compounds can target O-GlcNAcylation by regulating OGT to suppress oncogenesis. Taken together, targeting protein O-GlcNAcylation might be a promising strategy for the treatment of human malignancies.