Bringing to Light the Risk of Colorectal Cancer in Inflammatory Bowel Disease: Mucosal Glycosylation as a Key Player

Abstract Colitis-associated cancer is a major complication of inflammatory bowel disease remaining an important clinical challenge in terms of diagnosis, screening, and prognosis. Inflammation is a driving factor both in inflammatory bowel disease and cancer, but the mechanism underlying the transition from colon inflammation to cancer remains to be defined. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated both with colon inflammation and colorectal cancer development. In this review, we discuss the major molecular mechanisms of colitis-associated cancer pathogenesis, highlighting the role of glycans expressed at gut epithelial cells, at lamina propria T cells, and in serum proteins in the regulation of intestinal inflammation and its progression to colon cancer, further discussing its potential clinical and therapeutic applications. Lay Summary Colitis-associated cancer (CAC) is a major complication of inflammatory bowel disease and the molecular mechanisms underlying CAC progression are still elusive. Protein glycosylation holds a great promise for improving the understanding of CAC immunopathogenesis, opening new avenues for clinical and therapeutic interventions.