Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
FEBS Lett. 2020 Nov;594(22):3583-3601. doi: 10.1002/1873-3468.13933. Epub 2020 Oct 4.
Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to a family of G protein-coupled receptors (S1P ) and intracellular targets, such as HDAC1/2, that are functional in normal and pathophysiologic cell biology. There is a significant role for sphingosine 1-phosphate in cancer underpinning the so-called hallmarks, such as transformation and replicative immortality. In this review, we survey the most recent developments concerning the role of sphingosine 1-phosphate receptors, sphingosine kinase and S1P lyase in cancer and the prognostic indications of these receptors and enzymes in terms of disease-specific survival and recurrence. We also provide evidence for identification of new therapeutic approaches targeting sphingosine 1-phosphate to prevent neovascularisation, to revert aggressive and drug-resistant cancers to more amenable forms sensitive to chemotherapy, and to induce cytotoxicity in cancer cells. Finally, we briefly describe current advances in the development of isoform-specific inhibitors of sphingosine kinases for potential use in the treatment of various cancers, where these enzymes have a predominant role. This review will therefore highlight sphingosine 1-phosphate signalling as a promising translational target for precision medicine in stratified cancer patients.
鞘氨醇 1-磷酸（S1P）是一种具有生物活性的脂质，可与 G 蛋白偶联受体（S1P）家族和细胞内靶标（如 HDAC1/2）结合，这些靶标在正常和病理生理细胞生物学中具有功能。鞘氨醇 1-磷酸在癌症中具有重要作用，为所谓的特征提供了基础，例如转化和复制永生。在这篇综述中，我们调查了关于鞘氨醇 1-磷酸受体、鞘氨醇激酶和 S1P 裂解酶在癌症中的作用以及这些受体和酶在疾病特异性生存和复发方面的预后意义的最新进展。我们还提供了证据，证明了针对鞘氨醇 1-磷酸的新治疗方法的鉴定，以防止新血管生成，使侵袭性和耐药性癌症恢复为对化疗更敏感的更易于治疗的形式，并诱导癌细胞的细胞毒性。最后，我们简要描述了鞘氨醇激酶同工型特异性抑制剂在各种癌症治疗中的开发进展，这些酶在这些癌症中具有主要作用。因此，本综述将强调鞘氨醇 1-磷酸信号作为分层癌症患者精准医学有前途的转化靶标。
