Deoxycholic acid impairs glycosylation and fucosylation processes in esophageal epithelial cells.
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.
Cell and Molecular Biology, Department of Clinical Medicine, Trinity College, Dublin, Ireland. byrnea13@tcd.ie
Anne-Marie
AM
Byrne
Ruchika
R
Sharma
Gina
G
Duggan
Dermot
D
Kelleher
Aideen
A
Long
D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D004947:Esophagus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005643:Fucose / Q000378:metabolism*; D006031:Glycosylation; D006056:Golgi Apparatus / Q000187:drug effects; D006801:Humans
D015820:Cadherins; D003840:Deoxycholic Acid; D005643:Fucose; D066246:ErbB Receptors