Since we for the first time reported an oncogenic potential of sphingosine kinase-1 (SphK1) (Xia, et al.Current Biology, 2000), an increasing body of evidence has suggested a critical pathogenic role for SphK1 in a variety of human cancers.Upon activation, SphK1 catalyses the formation of sphingosine 1-phosphate (S1P) that serves as important signaling molecule in regulating cell survival, proliferation, differentiation, cellular motility and evasion of apoptosis, all key cellular processes in cancer development and progression.Over the past decade, our group has focused on understanding the activation mechanism of SphK1 and its role in cancer.We have demonstrated that the oncogenic activity of SphK1 entirely relies on its phosphorylation-dependent translocation to the plasma membrane beyond the enzymatic activity (Pitson, et al.JEM, 2005), and that this pathway can be activated by a wide variety of oncogenes or oncogenic factors.