The role of protein glycosylation in colorectal cancer: From molecular pathways to clinical applications

Glycosylation, a pivotal post-translational modification, critically influences colorectal cancer (CRC) progression via dysregulated N- and O-linked pathways, characterized by oligomannose, fucosylation, hypersialylation, truncated O-glycans (Tn, sialyl-Tn), branched N-glycans, and Lewis antigens. These alterations promote tumor aggressiveness, immune evasion, and metastasis through glycoprotein remodeling (e.g., mucins, integrins) and dysregulating glycosyltransferases (such as Fut2, ST6GAL1). Clinically, tumor-associated glycans offer diagnostic potential, with glycomic profiling enhancing early detection. Glycosylation further orchestrates the CRC microenvironment by modulating interactions among tumor cells, microbiota, and immune components. This review focuses exclusively on protein-centric glycosylation and highlights current studies on the roles of glycosylation in CRC, encompassing molecular mechanisms, diagnostic biomarkers, and emerging therapeutic strategies targeting glycosylation enzymes or glycan epitopes. Understanding glycan dysregulation provides new perspectives for biomarker development and targeted interventions in precision oncology.