FOXO3 and central nervous system cancer: As shown in Figure 5E, the phosphoryaltion level of Akt was upregulated by overexpression of SPHK1 and downregulated when SPHK1 was knocked down in U87MG and LN-382 glioma cells, suggesting a potential role of Akt in the signaling cascade that mediates FOXO3a phosphorylation/inactivation in response to SPHK1 upregulation.