Pyne Nigel J, Ohotski Jan, Bittman Robert, Pyne Susan
Cell Biology Research Group, Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
Cell Biology Research Group, Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
Adv Biol Regul. 2014 Jan;54:121-9. doi: 10.1016/j.jbior.2013.08.005. Epub 2013 Sep 11.
The enzymes that catalyze formation of the bioactive sphingolipid, sphingosine 1-phosphate, sphingosine kinase 1 and 2, are predictive markers in inflammatory diseases and cancer as evidenced by data from patients, knockout mice and the use of available molecular and chemical inhibitors. Thus, there is a compelling case for therapeutic targeting of sphingosine kinase. In addition, there are several examples of functional interaction between sphingosine 1-phosphate receptors and sphingosine kinase 1 that can drive malicious amplification loops that promote cancer cell growth. These novel aspects of sphingosine 1-phosphate pathobiology are reviewed herein.
催化生物活性鞘脂——1-磷酸鞘氨醇形成的酶,即鞘氨醇激酶1和2,在炎症性疾病和癌症中是预测性标志物,来自患者、基因敲除小鼠的数据以及现有分子和化学抑制剂的使用都证明了这一点。因此,有令人信服的理由将鞘氨醇激酶作为治疗靶点。此外,1-磷酸鞘氨醇受体与鞘氨醇激酶1之间存在多种功能相互作用的例子,这些相互作用可驱动促进癌细胞生长的恶性放大循环。本文将对1-磷酸鞘氨醇病理生物学的这些新方面进行综述。