文章：

鞘脂代谢通路在肝脏再生、肝细胞癌进展及治疗中的关键作用

Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy

原文发布日期：20 February 2024

DOI: 10.3390/cancers16050850

类型: Article

开放获取: 是

英文摘要：

The sphingolipid metabolic pathway, an important signaling pathway, plays a crucial role in various physiological processes including cell proliferation, survival, apoptosis, and immune regulation. The liver has the unique ability to regenerate using bioactive lipid mediators involving multiple sphingolipids, including ceramide and sphingosine 1-phosphate (S1P). Dysregulation of the balance between sphingomyelin, ceramide, and S1P has been implicated in the regulation of liver regeneration and diseases, including liver fibrosis and hepatocellular carcinoma (HCC). Understanding and modulating this balance may have therapeutic implications for tumor proliferation, progression, and metastasis in HCC. For cancer therapy, several inhibitors and activators of sphingolipid signaling, including ABC294640, SKI-II, and FTY720, have been discussed. Here, we elucidate the critical roles of the sphingolipid pathway in the regulation of liver regeneration, fibrosis, and HCC. Regulation of sphingolipids and their corresponding enzymes may considerably influence new insights into therapies for various liver disorders and diseases.

摘要翻译： 

鞘脂代谢通路作为重要的信号传导途径，在细胞增殖、存活、凋亡及免疫调节等多种生理过程中发挥关键作用。肝脏具有独特的再生能力，这一过程涉及包括神经酰胺和1-磷酸鞘氨醇（S1P）在内的多种生物活性脂质介质。鞘磷脂、神经酰胺与S1P之间的平衡失调已被证实与肝脏再生及肝纤维化、肝细胞癌（HCC）等疾病的调控密切相关。理解并调控这一平衡可能对HCC的肿瘤增殖、进展及转移具有治疗意义。在癌症治疗领域，包括ABC294640、SKI-II和FTY720在内的多种鞘脂信号通路抑制剂与激活剂已被广泛探讨。本文系统阐述了鞘脂通路在调控肝脏再生、纤维化及HCC中的关键作用。通过调控鞘脂及其相关酶活性，可能为多种肝脏疾病的治疗策略提供新的研究方向。

原文链接：

Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy