Thus, these findings suggest that SPNS2 mediates metastasis of CRC via inhibiting EMT and has potential to be a novel molecular target for anti-metastasis therapy in CRC.PI3K/Akt, JAK/STAT3 and ERK are reported to be simulated by SPNS2 via extracellular S1P/S1PRs combination in cancer cells. Here, SPNS2 is linked to cancer.