Reduced αGlcNAc glycosylation on gastric gland mucin is a biomarker of malignant potential for gastric cancer, Barrett’s adenocarcinoma, and pancreatic cancer
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Gastric gland mucin secreted from pyloric gland cells, mucous neck cells, and cardiac gland cells of the gastric mucosa harbors unique O-glycans carrying terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc), which are primarily attached to the scaffold mucin core protein MUC6. αGlcNAc acts as an antibiotic against Helicobacter pylori (H. pylori), a microbe causing gastric cancer. In addition, mice deficient in A4gnt, which encodes the enzyme α1,4-N-acetylglucosaminyltransferase (α4GnT) that catalyzes αGlcNAc biosynthesis, spontaneously develop gastric differentiated-type adenocarcinoma, even if not infected by H. pylori. Thus, αGlcNAc prevents gastric cancer as both an antibiotic and a tumor suppressor (Nakayama in Acta Histochem Cytochem 47:1–9, 2014b). Indeed, in humans αGlcNAc loss on MUC6 in differentiated-type adenocarcinoma is closely associated with poor patient prognosis (Shiratsu et al. in Cancer Sci 105:126–133, 2014). Recently, we reported reduced αGlcNAc expression on MUC6 in both pyloric gland adenoma of the stomach and chronic atrophic gastritis, in Barrett’s esophagus, and in pancreatic intraductal papillary-mucinous neoplasm (IPMN)/pancreatic intraepithelial neoplasia (PanIN), all potentially premalignant conditions. This review discusses whether relatively reduced levels of αGlcNAc in these lesions could serve as a biomarker to predict malignant potential and cancer progression.
KeywordsBarrett’s esophagus Chronic atrophic gastritis Immunohistochemistry IPMN/PanIN O-glycan, Pyloric gland adenoma
The authors are grateful to all collaborators for their contribution to research relevant to the gastric gland mucin-specific O-glycan αGlcNAc. The authors also thank Dr. Elise Lamar for editing the manuscript.
Grants-in-Aid for Scientific Research 15H04712 and 17K15640 from the Japan Society for the Promotion of Science.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest in association with the present study.
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