Fig. 6

The mechanism underlying the RPTOR-promoted NSCLC-BM via the SPHK2/S1P/STAT3 signaling pathway. RPTOR regulated the transcriptional activation of the ceramidase SPHK2 by binding to the transcription factor YY1. SPHK2 catalyzed the degradation of ceramide to S1P. The latter, in turn, activated the STAT3 signaling pathway by binding to S1PR1 (solid lines), altering the microenvironment and enhancing the permeability of the BBB (dotted lines), resulting in the BM of NSCLC