Owing to the fact that recent studies suggest that exogenous S1P could regulate adaptation to hypoxia through the content of HIF-1α in cancer24, 34 and non-cancer cells,47 we examined the contribution of extracellular S1P in the regulation of HIF-2α in our ccRCC cell models. The gene discussed is HIF1A; the disease is nonpapillary renal cell carcinoma.