The antioxidant enzyme glutathione peroxidase 7 (GPX7) is often “turned off” in esophageal adenocarcinoma and its precancerous condition known as Barrett’s esophagus.
Wael El-Rifai, M.D., Ph.D., DunFa Peng, Ph.D., and colleagues previously showed that GPX7’s antioxidant properties protect esophageal cells against oxidative damage. Now, in the journal Gut, they report that the enzyme also has tumor suppressor functions.
Restoring GPX7 in esophageal cancer cell lines suppressed cell growth by turning on cell cycle regulators, and cells with restored GPX7 had reduced tumor growth in an animal model. The researchers demonstrated that epigenetic hypermethylation (a chemical modification) of a specific promoter region – but not genetic mutations or gene loss – was associated with silencing of GPX7 in esophageal cancer cells.
Combined with previous results, the study shows that GPX7 functions both as an antioxidant and as a tumor suppressor and suggests that patients diagnosed with Barrett’s esophagus with loss of GPX7 may be at higher risk of progression to esophageal cancer.
This research was supported by grants from the National Institutes of Health (CA106176), the Department of Veterans Affairs, the Vanderbilt SPORE in Gastrointestinal Cancer (CA095103), the Vanderbilt-Ingram Cancer Center (CA068485) and the Vanderbilt Digestive Disease Research Center (DK058404).