Hypoxia increases the production and release of S1P in glioma cells [60], upregulates SphK1 that promotes the migration of endothelial cells [60], stimulates SphK2 expression and S1P release in adenocarcinoma cells [61], and stimulates SphK1 and SphK2 expression in pulmonary smooth muscle cells [62]. Here, SPHK1 is linked to central nervous system cancer.