{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Fucosyltransferase‐3 (FUT3) is a key enzyme that catalyzes the α1,3/1,4‐fucosylation of glycan precursors to generate a variety of Lewis blood group antigens – including Lewis a, Lewis x, Lewis y, and their sialylated forms – which are critical determinants of cell–cell recognition, adhesion, and signaling. FUT3‐mediated fucosylation modulates the cell surface glycome in multiple biological contexts. In cancer, up‐regulation of FUT3 contributes to the enhanced expression of sialyl Lewis x epitopes that promote E‐selectin–dependent adhesion, facilitate tumor cell rolling on the endothelium, and thereby support metastatic dissemination in several malignancies such as breast, colon, gastric, and prostate cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, FUT3 expression is dynamically regulated by both epigenetic and transcriptional mechanisms – as evidenced by its up‐regulation during epithelial–mesenchymal transition mediated by factors including c‐Myc, and by promoter hypomethylation in gastric carcinoma cells – which in turn alters the biosynthesis of glycan epitopes such as disialyl Lewis a and influences serum biomarkers like CA19-9."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition to its roles in tumor progression, FUT3 has been implicated in modulating host–microbe interactions via the expression of histo‐blood group antigens and in influencing cellular responses to apoptotic stimuli; for example, alterations in FUT3 expression can affect signaling through fucosylated receptors such as TGFβR-I, thereby impacting pathways involved in cell survival and sensitivity to TRAIL‐mediated apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Finally, genetic polymorphisms in the FUT3 gene contribute to the Lewis-negative phenotype observed in diverse populations and have important implications for disease susceptibility and the interpretation of glycan-based biomarkers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sylvain Julien, Aleksandar Ivetic, Anita Grigoriadis, et al. 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