Genetic variations in G protein–coupled receptor 35 (GPR35) are associated with an increased risk for primary sclerosing cholangitis (PSC) and related cancers however the general function of GPR35 is poorly understood.
Using Gpr35-deficient mice, we found that GPR35 promotes the activity of sodium/potassium-ATPase, a ubiquitous and essential transmembrane pump that regulates cellular metabolism and proliferation.
A genetic variant of GPR35 associated with PSC heightens sodium/potassium-ATPase activity, enhancing glycolysis and proliferation of intestinal epithelial cells compared to non-PSC-associated GPR35.
Intriguingly, treatment reducing GPR35 activity decreased tumor burden in mice suggesting that GPR35 could be an attractive target for the treatment of PSC and related cancers.
For more information, please see: http://stke.sciencemag.org/content/12/562/eaau9048