MTOR and tongue neoplasm: Based upon the findings that p-AKT (ser473) was reduced in tongue tumors induced by 4-NQO in SphK1 KO mice [11] and mTOR inhibitor, rapamycin, significantly reduced malignant conversion of precancerous lesions and promoted regression of 4-NQO induced oral carcinogenesis [72], Shirai et al. [11] postulates that SphK1/S1P modulates downstream AKT signaling and plays a role in dysregulating mTOR signaling.