Deoxycholic acid impairs glycosylation and fucosylation processes in esophageal epithelial cells.
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2012Access:
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Byrne, A.M., Sharma, R., Duggan, G., Kelleher, D. & Long, A., Deoxycholic acid impairs glycosylation and fucosylation processes in esophageal epithelial cells., Glycobiology, 22, 5, 2012, 638-648Download Item:
Abstract:
It is generally accepted that esophageal adenocarcinoma arises from a Barrett's metaplastic lesion. Altered glycoprotein expression has been demonstrated in tissue from patients with Barrett's esophagus and esophageal cancer but the mechanisms regarding such changes are unknown. The bile acid deoxycholic acid (DCA) alters many cell signaling pathways and is implicated in esophageal cancer progression. We have demonstrated that DCA disrupts Golgi structure and affects protein secretion and glycosylation processes in cell lines derived from normal squamous epithelium (HET-1A) and Barrett's metaplastic epithelium (QH). Cell surface expression of glycans was identified using carbohydrate-specific probes (wheat germ agglutinate, conconavalin A, peanut agglutinin, lithocholic acid and Ulex europaeus agglutinin) that monitored N-glycosylation, O-glycosylation and core fucosylation in resting and DCA-treated cells. DCA altered intracellular localization and reduced cell surface expression of N-acetyl-d-glucosamine, α-methyl-mannopyranoside (Man/Glc) and fucose in both cell lines. Furthermore, DCA reduced the expression of epithelial growth factor receptor and E-cadherin in a manner analogous to treatment of cells with the N-glycan biosynthesis inhibitor tunicamycin. This is the first study to identify an altered Golgi structure and glycomic profile in response to DCA in esophageal epithelial cells, a process which could potentially contribute to metaplasia, dysplasia and cancer of the esophagus.
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http://people.tcd.ie/longaihttp://people.tcd.ie/kellehdp
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Glycobiology;22;
5;
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Barrett's esophagus, Bile acid, E-cadherin, Glycosylation, Esophageal cancerDOI:
http://dx.doi.org/10.1093/glycob/cwr190Metadata
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