SPHK1 and breast cancer: S1P not only functions intracellularly as a second messenger, but also can be exported extracellularly to serve as a ligand for a family of S1P receptors.367 S1P promotes lymphangiogenesis both in vitro and in vivo through the S1P/Gi/phospholipase C/Ca2+ signaling pathways.368 In breast cancer, SphK1-mediated S1P production induced lymphangiogenesis, indicating that SphK1-S1P signaling may be a potential therapeutic target for controlling lymphangiogenesis.369