Glycosaminoglycans in gastrointestinal cancer: from biosynthesis to tumor signatures

Glycosaminoglycans (GAGs) are major components of the cells glycocalyx and extracellular matrix (ECM), with important roles in both physiological and disease contexts. The biosynthesis of the long and structurally diverse GAG chains is orchestrated by a complex cellular glycosylation machinery and regulated in an organ-, and cell-specific way. Moreover, altered GAG expression levels and structural features have been described in different pathological conditions, including cancer. Noteworthy, GAG chains are endowed with important functional features during cancer progression, such as cancer cell growth, motility, and metastasis formation. Particularly in gastrointestinal (GI) tumors, GAGs have been frequently associated with tumorigenesis and disease progression. This review provides insights on the aberrant GAG expression profiles in GI cancers, highlighting illustrative examples of GAG structural features for each disease model. Relevance is given to the molecular mechanisms underlying altered GAG biosynthesis and post-synthesis editing in GI cancers. Lastly, we address the potential of cancer-associated GAG expression signatures for improving GI clinical management.