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Mucin-3 (MUC3) is a high-molecular-weight transmembrane glycoprotein primarily expressed in the intestinal and gallbladder epithelia, where it forms a critical component of the protective glycocalyx [5, 13]. It is encoded by two closely related paralogous genes, MUC3A and MUC3B, which are characterized by extensive O-glycosylation and the presence of epidermal growth factor (EGF)-like domains in their extracellular regions [6, 7, 21]. MUC3 plays a dual role in epithelial biology: it acts as a physical barrier against pathogens and toxins while also participating in cell signaling pathways, particularly through its interaction with the epidermal growth factor receptor (EGFR) to promote cell survival and migration [2, 5]. In disease states, MUC3 is frequently dysregulated; its overexpression is linked to the progression and chemoresistance of colorectal, gastric, and pancreatic cancers, while its downregulation is associated with inflammatory bowel disease (IBD) [5, 11, 21]. Therapeutic targeting of MUC3 is an emerging area of research, with strategies including the use of small molecules like talniflumate, which inhibits the core mucin-synthesizing enzyme GCNT3 to disrupt mucin production and improve the efficacy of other chemotherapeutic agents [20, 35]. Additionally, experimental monoclonal antibodies are being developed to disrupt its signaling and adhesive functions in malignant tissues [30, 34].
Inhibition of mucin biosynthesis via GCNT3 (core 2 beta-1,6 N-acetylglucosaminyltransferase) inhibition; modulation of cell signaling pathways such as EGFR; physical barrier disruption to improve drug delivery.
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