Expression of the Endoplasmic Reticulum Oxidoreductase Ero1α in Gastro-Intestinal Cancer Reveals a Link Between Homocysteine and Oxidative Protein Folding

Aim: 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 Ero1 alpha in the digestive system and to examine the behavior of Ero1 alpha in premalignant Barrett's esophagus, esophageal (OE) and gastric cancers and esophageal cancer cell lines. Results: Ero1 alpha 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 Ero1 alpha in the OE cancer cell line OE33. Innovation: These results demonstrate for the first time that Ero1 alpha can sense the level of an amino acid precursor, identifying a potential link between diet, antioxidants, and oxidative protein folding in the ER. Conclusion: The high expression of Ero1 alpha 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.