According to our work, NSCLC cells with S1PR3 silence down-regulated PBX1 expression and induced G1 phase arrest, which failed to respond to the exogenous S1P stimulation, suggesting the bridge role of S1PR3 in the SPHK1/PBX1 axis-mediated cell function. The gene discussed is SPHK1; the disease is non-small cell lung carcinoma.