The addition of the SPHK2 inhibitor, ABC294640, to the RPTOR-overexpressed PC9 cells significantly inhibited the RPTOR-induced activation of the SPHK2/S1P/STAT3 signaling pathway (Fig. 3E) and restrained the RPTOR overexpression-enhanced proliferation, migration and invasion of lung cancer cell lines (Supplementary Fig. S4A, B). Here, SPHK2 is linked to lung cancer.