MAPK3 and cancer: Convincing evidence indicates that the activation of SPHK1 contributes to cancer progression and tumor growth and impairs cancer cell apoptosis via suppressing STAT1 expression (72), as well as activating the ERK1/2 and PI3K/AKT pathways (29) Many studies have demonstrated that the activation of SPHK1 can induce cancer cell migration, and that the SPHK1/S1P axis enhances the metastatic potential of cancer cells.