title: Expression of the endoplasmic reticulum oxidoreductase Ero1α in gastro-intestinal cancer reveals a link between homocysteine and oxidative protein folding.
abstract: OBJECTIVE
  Ero proteins are central to oxidative protein folding in the endoplasmic reticulum (ER), but their expression varies in a tissue-specific manner. The aim of this work was to establish the expression of Ero1α in the digestive system and to examine the behavior of Ero1α in premalignant Barrett's esophagus, esophageal (OE) and gastric cancers and esophageal cancer cell lines.
  
  
  RESULTS
  Ero1α is expressed in the columnar epithelium of Barrett's tissue, and in OE tumors and gastric tumors. Homocysteine, a precursor in the metabolism of cysteine and methionine, induces the active Ox1 form of Ero1α in the OE cancer cell line OE33.
  
  
  METHODS
  These results demonstrate for the first time that Ero1α can sense the level of an amino acid precursor, identifying a potential link between diet, antioxidants, and oxidative protein folding in the ER.
  
  
  CONCLUSIONS
  The high expression of Ero1α in cancers of the esophagus and stomach demonstrates the importance of ER redox regulation in the gastro-intestinal (GI) tract in health and disease. Proteins and metabolites involved in disulfide bond formation and redox regulation may be suitable targets for both biomarker and drug development in GI cancer.
authors: School of Biological and Biomedical Sciences, Durham University, Durham, England.
authors: Danielle M
authors: DM
authors: Battle
authors: Sanjika Dias
authors: SD
authors: Gunasekara
authors: Graeme R
authors: GR
authors: Watson
authors: Eltayeb Mohamed
authors: EM
authors: Ahmed
authors: Colin G
authors: CG
authors: Saysell
authors: Naveed
authors: N
authors: Altaf
authors: Abayomi L
authors: AL
authors: Sanusi
authors: Phanibhushana C
authors: PC
authors: Munipalle
authors: David
authors: D
authors: Scoones
authors: Julie
authors: J
authors: Walker
authors: Yks
authors: Y
authors: Viswanath
authors: Adam M
authors: AM
authors: Benham
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D004220:Disulfides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000201:enzymology* / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D017510:Protein Folding
chemical_list: D004220:Disulfides; D008562:Membrane Glycoproteins; D006710:Homocysteine; C405327:ERO1A protein, human; D010088:Oxidoreductases