SPHK1 and central nervous system cancer: Highly hypoxic human cancer cell models such as U87 glioma cells, clear cell renal cell carcinoma models (ccRCC) such as CAKI-1 and A498 and androgen-independent PC-3 cells have increased SK1 mRNA expression, SK1 and activity and, consequently, increased S1P secretion under hypoxic conditions [87,88,89].