O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible protein post-translational modification (PTM) that primarily regulates protein enzymatic activity (Olsen and Mann, 2013), subcellular localization, protein stability, transcriptional activity, and interactions with other proteins (Yang and Qian, 2017a, Whelan and Hart, 2003a). So far, approximately 3000 human proteins have been confirmed to be O-GlcNAcylation (Decourcelle et al., 2019). The disorder of O-GlcNAcylation circulation is related to the progression of various chronic human diseases, including aging, obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer (Hart et al., 2007, He et al., 2023). In recent years, O-GlcNAcylation has been reported to be closely related to the development of tumors (Ma and Vosseller, 2014). Imbalances in O-GlcNAcylation levels have been found in different types of cancer (Spaner, 2021), leading to various cancer markers such as tumor growth, metastasis, angiogenesis, cancer stemness potential, and metabolic reprogramming (Hart et al., 2011). Therefore, exploring the specific mechanism of O-GlcNAcylation in tumors is very significant.

The innate immune response is initiated by pattern recognition receptors (PRRs) (Biwi et al., 2018), which recognize the presence of unique microbial components (Xia et al., 1997), namely pathogens. They are the first line of defense against pathogen invasion and maintain internal balance (Mantovani et al., 2021). The release of endogenous stress-induced molecular patterns or damage-related molecular patterns activates downstream inflammatory pathways, eliminates microbial infections (Haas and Obenauf, 2019), and repairs damaged tissues (Erez et al., 2010). Chronic inflammation is correlated with the risk of cancer progression (Singh et al., 2019). Cancer cells absorb a large amount of glucose and glutamine to maintain storage pools of various carbon intermediates (Coussens and Werb, 2002). Unlike normal cells, the cellular metabolism of cancer cells changes to meet the increasing biosynthetic and energy demands of tumors (Kennel et al., 2023). These metabolic changes accelerate the production of molecules (Murata, 2018), such as lactate and reactive oxygen species while also aiding the inflammatory environment. If inflammation is not regulated and becomes chronic (Khandia and Munjal, 2020), inflammatory cells will infiltrate the tumor microenvironment (TME) (Mantovani et al., 2008), produce inflammatory mediators, such as growth factors (Katoh, 2018), cytokines, and chemokines (Diakos et al., 2014), and stimulate the initiation and malignant growth of tumors.

In this article, we mainly focus on the latest research on the relationship between O-GlcNAcylation and cancer-related inflammation and provide an overview of how O-GlcNAcylation drives the potential mechanisms of inflammation in tumors, the environmental environment, and its relationship with cancer progression.