Roles of sphingolipid metabolism on cell death by necroptosis

鞘氨醇激酶(SPHK)催化鞘氨醇的磷酸化生成鞘氨醇-1-磷酸，在哺乳动物中有两种亚型，SPHK1和SPHK2。这两种同工酶都是很有前景的抗癌治疗靶点。在这项研究中，我们发现鞘氨醇和作为SPHK2抑制剂的神经鞘氨醇的合成类似物SG-12分别通过SPHK1和SPHK2的磷酸化诱导细胞死亡。目前的结果揭示了一种鞘氨醇类似物在SPHK2上调的病理环境中的新的抗癌潜力。

Sphingosine kinase (SPHK), which catalyzes the phosphorylation of sphingosine to generate sphingosine-1-phosphate, has two mammalian isotypes, SPHK1 and SPHK2. Both isozymes are promising anti-cancer therapeutic targets. In this study, we found that sphingosine and SG-12, a synthetic analogue of sphingosine that acts as a SPHK2 inhibitor, induce cell death via phosphorylation by SPHK1 and SPHK2, respectively. The present results revealed the novel anti-cancer potential of a sphingosine analogue in the pathological setting where SPHK2 is upregulated.