Alpha-1,4-N-Acetylglucosaminyltransferase (A4GNT)

Nakayama, Jun

doi:10.1007/978-4-431-54240-7_87

Cited by 3 publications

(3 citation statements)

References 22 publications

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“…Previously, we isolated human cDNA encoding α4GnT, which catalyzes αGlcNAc biosynthesis by transferring GlcNAc from UDP-GlcNAc to terminal β-galactose residues present in O -glycans with an α1,4-linkage (Fig. 1) 26,27 . α4GnT protein is localized to the Golgi apparatus of gastric gland mucous cells, which corresponds to its expression as “dot-like” pattern (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we observe that MUC6 but not α4GnT is frequently expressed in NNEG. In humans, chromosomal locations of MUC6 and α4GnT are 11p15.5 and 3q22.3, respectively, strongly suggesting that both genes are regulated separately 27,34 . It is possible that NNEG expressing MUC6 alone could be phenotypically regarded as an incomplete pyloric gland metaplasia-like lesion, while LEGH expressing both α4GnT/αGlcNAc and MUC6 could be seen as a complete pyloric gland metaplasia-like lesion.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we isolated cDNA encoding α1,4- N -acetylglucosaminyltransferase (α4GnT), the enzyme catalyzing αGlcNAc biosynthesis (Fig. 1), and then generated A4gnt -deficient mice 26,27 . These mutant mice showed αGlcNAc loss in gastric gland mucin and naturally developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence without Helicobacter pylori infection 28 .…”

Section: Introductionmentioning

confidence: 99%

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αGlcNAc and its catalyst α4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type

Ito

Yamanoi

Asaka

et al. 2019

Sci Rep

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Cervical adenocarcinoma, gastric type (GAS) is not associated with human papilloma virus (HPV) infection. GAS patients prognoses are significantly worse compared with cervical adenocarcinoma associated with HPV infection, as their tumors exhibit resistance to conventional chemotherapy and radiotherapy. GAS is often associated with lobular endocervical glandular hyperplasia (LEGH), which is regarded as a precursor to GAS in the latest WHO classification. Recently, we reported that a decrease in expression of terminal α1,4-linked N-acetylglucosamine (αGlcNAc) relative to that of MUC6 was already apparent in atypical LEGH in the LEGH-GAS sequence. Here, we analyzed expression of α1,4-N-acetylglucosaminyltransferase (α4GnT), the sole enzyme catalyzing αGlcNAc biosynthesis, and that of αGlcNAc and MUC6 in cases representing non-neoplastic endocervical gland (NNEG) (11 cases), LEGH (26 cases) and GAS (12 cases). α4GnT protein was detected in a “dot-like” pattern, indicating localization in the Golgi apparatus in all 26 LEGH cases and 5 of 12 GAS cases. α4GnT- and αGlcNAc-positive cells largely overlapped, suggesting that α4GnT gene expression regulates αGlcNAc biosynthesis. Interestingly, all NNEG cases were negative for α4GnT and αGlcNAc expression, but 7 of 11 NNEG and all LEGH cases were MUC6-positive. In GAS cases, patients whose tumors were α4GnT- and αGlcNAc-positive had more favorable prognosis than others. Multivariate analysis revealed that positive expressions of α4GnT and αGlcNAc were independent prognostic indicators. These results indicate that α4GnT and αGlcNAc could serve as useful markers not only to distinguish LEGH from NNEG but to evaluate prognoses of GAS patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

αGlcNAc and its catalyst α4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type

Ito

Yamanoi

Asaka

et al. 2019

Sci Rep

Self Cite

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Reduced αGlcNAc glycosylation on gastric gland mucin is a biomarker of malignant potential for gastric cancer, Barrett’s adenocarcinoma, and pancreatic cancer

Yamanoi

Nakayama

2018

Histochem Cell Biol

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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.

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Trefoil factors share a lectin activity that defines their role in mucus

et al. 2020

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The mucosal epithelium secretes a host of protective disulfide-rich peptides, including the trefoil factors (TFFs). The TFFs increase the viscoelasticity of the mucosa and promote cell migration, though the molecular mechanisms underlying these functions have remained poorly defined. Here, we demonstrate that all TFFs are divalent lectins that recognise the GlcNAc-α-1,4-Gal disaccharide, which terminates some mucin-like O-glycans. Degradation of this disaccharide by a glycoside hydrolase abrogates TFF binding to mucins. Structural, mutagenic and biophysical data provide insights into how the TFFs recognise this disaccharide and rationalise their ability to modulate the physical properties of mucus across different pH ranges. These data reveal that TFF activity is dependent on the glycosylation state of mucosal glycoproteins and alludes to a lectin function for trefoil domains in other human proteins.

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Alpha-1,4-N-Acetylglucosaminyltransferase (A4GNT)

Cited by 3 publications

References 22 publications

αGlcNAc and its catalyst α4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type

αGlcNAc and its catalyst α4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type

Reduced αGlcNAc glycosylation on gastric gland mucin is a biomarker of malignant potential for gastric cancer, Barrett’s adenocarcinoma, and pancreatic cancer

Trefoil factors share a lectin activity that defines their role in mucus

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