Mechanistically, our data indicate that S1P can activate MAPK pathway but not Akt or JAK‐STAT pathway in PCa (Figure 4A and B and Supporting information Figure S4A‐C) to increase REST phosphorylation at S861/864 sites leading to a rapid turnover by proteasome degradation (Figure 4C‐E and Supporting information Figure S4E‐F). This evidence concerns the gene SOAT1 and posterior cortical atrophy.