Role of Sphingosine Kinase 1 and Sphingosine-1-Phosphate Axis in Hepatocellular Carcinoma
Role of Sphingosine Kinase 1 and Sphingosine-1-Phosphate Axis in Hepatocellular Carcinoma
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DOI：
10.1007/164_2019_217
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发表时间：
2020-01-01
期刊：
影响因子：
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通讯作者：
Spiegel, Sarah
中科院分区：
文献类型：
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作者：
Maceyka, Michael;Rohrbach, Timothy;Spiegel, Sarah
肝细胞癌（HCC）主要在疾病进展的后期被诊断出来，是全球癌症死亡的第三大原因。因此，有必要发现早期HCC的生物标志物，并开发更有效的治疗方法。鞘氨醇-1-磷酸（S1P）是一种多效性脂质信号分子，由鞘氨醇激酶的两种异构体（SphK1和SphK2）产生，参与哺乳动物生理和病理生理的许多方面的调节，包括炎症、上皮和内皮屏障功能、癌症和转移等。大量证据表明，SphK1和S1P促进多种类型癌症的进展和转移。然而，SphK/S1P在HCC中的作用研究较少。在这里，我们回顾了SphK1和S1P在HCC中的知识现状，包括SphK1表达和S1P水平与HCC进展和阴性结果相关的证据，并讨论了这些信息如何导致设计更有效的HCC诊断和治疗方式。
Hepatocellular carcinoma (HCC) is primarily diagnosed in the latter stages of disease progression and is the third leading cause of cancer deaths worldwide. Thus, there is a need to find biomarkers of early HCC as well as the development of more effective treatments for the disease. Sphingosine-1-phosphate (S1P) is a pleiotropic lipid signaling molecule produced by two isoforms of sphingosine kinase (SphK1 and SphK2) that is involved in regulation of many aspects of mammalian physiology and pathophysiology, including inflammation, epithelial and endothelial barrier function, cancer, and metastasis, among many others. Abundant evidence indicates that SphK1 and S1P promote cancer progression and metastasis in multiple types of cancers. However, the role of SphK/S1P in HCC is less well studied. Here, we review the current state of knowledge of SphKs and S1P in HCC, including evidence for the correlation of SphK1 expression and S1P levels with progression of HCC and negative outcomes, and discuss how this information could lead to the design of more effective diagnostic and treatment modalities for HCC.