Dual Roles of Gastric Gland Mucin-specific <i>O</i>-glycans in Prevention of Gastric Cancer

Abstract

Gastric gland mucin is secreted from gland mucous cells, including pyloric gland cells and mucous neck cells located in the lower layer of the gastric mucosa. These mucins typically contain O-glycans carrying terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc) attached to the scaffold protein MUC6, and biosynthesis of the O-glycans is catalyzed by the glycosyltransferase, α1,4-N-acetylglucosaminyltransferase (α4GnT). We previously used expression cloning to isolate cDNA encoding α4GnT, and then demonstrated that αGlcNAc functions as natural antibiotic against Helicobacter pylori, a microbe causing various gastric diseases including gastric cancer. More recently, it was shown that αGlcNAc serves as a tumor suppressor for differentiated-type adenocarcinoma. This review summarizes these findings and identifies dual roles for αGlcNAc in gastric cancer.

Gastric gland mucin‐specific O‐glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer

“…We then reported that Α4gnt ‐deficient mice, which show αGlcNAc loss in gland mucin, spontaneously develop gastric adenocarcinoma . These findings suggest that αGlcNAc serves as a tumor suppressor . In support of this idea, we observed that αGlcNAc expression is frequently lost in human gastric differentiated‐type adenocarcinoma expressing MUC6 .…”

Decreased expression of gastric gland mucin‐specific glycan α1,4‐linked N‐acetylglucosamine on its scaffold mucin 6 is associated with malignant potential of pyloric gland adenoma of the stomach

“…Surprisingly, mutant mice developed gastric adenocarcinoma through a hyperplasia–dysplasia–carcinoma sequence, even in the absence of H. pylori infection, indicating that αGlcNAc is directly associated with gastric tumorigenesis independently of H. pylori infection. Collectively, these results indicate that αGlcNAc plays dual roles in preventing gastric cancer …”

Comparative glycopattern analysis of mucins in the Brunner's glands of the guinea-pig and the house mouse (Rodentia)

“…WGA-binding is partially due to sialic acid, since this lectin binds to both sialic acid and GlcNAc (Gallagher et al, 1985) and binding intensity decreased after sialidase. Terminal GlcNAc was confirmed by the presence of stable class-III mucins, as evidenced by PCS: according to Nakayama (2014), these mucins are O-glycans having terminal ␣1,4-linked GlcNAc. Binding of PNA and RCA-I can be explained by the presence of terminal Gal residuals linked to GalNAc and GlcNAc, respectively.…”

“…In any case, the Guinea-pig's Brunner glands seem capable to modulate the relative amounts of sulfated and sialylated residues in their secretion, possibly in relation to physiological or pathological conditions. Another residual in the oligosaccharidic chains important in the prevention of pathologies is terminal ␣1,4-linked GlcNAc, as evidenced by the PCS method, which acts both as a natural antibiotic and as a tumor suppressor for differentiated-type adenocarcinoma (Nakayama, 2014). GlcNAc is also an important site for the linking of acidic residuals (Holmen Larsson et al, 2013).…”