Abstract
Cancer Polymorphisms in the G protein–coupled receptor GPR35 are associated with increased risk for certain inflammatory diseases that can progress to cancer. Schneditz et al. found that GPR35 promoted the activity of Na+- and K+-dependent adenosine triphosphatase (Na+,K+-dependent ATPase), a transmembrane pump that sets the membrane potential in cells. This effect was enhanced by a disease-associated GPR35 variant. Stimulation of Na+,K+-ATPase activity by GPR35 increased glycolysis and proliferation in intestinal epithelial cells. Na+,K+-ATPase deficiency or treatment with a pepducin targeting GPR35 decreased tumor burden in mouse models of intestinal cancer. Sci. Signal. 12 , eaau9048 (2019).
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