文章：

生物活性鞘脂在癌症发病和治疗中的作用

Biologically active sphingolipids in cancer pathogenesis and treatment

原文发布日期：2004-08-01

DOI: 10.1038/nrc1411

类型: Review Article

开放获取: 否

要点：

1. The sphingolipids ceramide and sphingosine-1-phosphate (S1P) function as effector molecules, and have important roles in stimulus/agonist-mediated signalling and the regulation of many cellular processes.
2. Ceramide, the central molecule in sphingolipid metabolism, mediates antiproliferative responses such as growth inhibition, apoptosis, differentiation, modulation of telomerase activity and telomere length, and senescence. Conversely, S1P induces proliferation, transformation, angiogenesis and cell motility.
3. A network of specialized and compartmentalized enzymes regulates the levels of ceramide and S1P. These enzymes serve as transducers that couple the actions of numerous extra- and intracellular signals to sphingolipid-mediated responses.
4. Attenuation of ceramide levels and/or increased levels of S1P are increasingly implicated in various stages of cancer pathogenesis, including an anti-apoptotic phenotype, metastasis and escape from senescence.
5. Small-molecule inhibitors of enzymes involved in ceramide clearance specifically induce ceramide accumulation and could present a novel therapeutic modality for the treatment of human cancers, including the reversal of drug resistance.

要点翻译：

1. 鞘脂类中的神经酰胺和1-磷酸鞘氨醇（S1P）作为效应分子，在刺激/激动剂介导的信号传导及多种细胞过程调控中发挥重要作用。
2. 作为鞘脂代谢的核心分子，神经酰胺介导抗增殖反应，如生长抑制、细胞凋亡、分化、端粒酶活性与端粒长度的调控以及细胞衰老。相反，S1P则诱导增殖、转化、血管生成和细胞运动。
3. 由特异化且区室化的酶构成的网络调控着神经酰胺和S1P的水平。这些酶作为转导器，将众多细胞外和细胞内信号的作用与鞘脂介导的反应相耦合。
4. 神经酰胺水平的下调和/或S1P水平的升高日益被证实与癌症发病机制的多个阶段相关，包括抗凋亡表型、转移及衰老逃逸等现象。
5. 针对神经酰胺清除相关酶的小分子抑制剂能特异性诱导神经酰胺积聚，可能为人类癌症（包括逆转耐药性）提供一种新型治疗策略。

英文摘要：

Biologically active sphingolipids have key roles in the regulation of several fundamental biological processes that are integral to cancer pathogenesis. Recent significant progress in understanding biologically active sphingolipid synthesis, specifically within ceramide and sphingosine-1-phosphate (S1P)-mediated pathways, has identified crucial roles for these molecules both in cancer development and progression. Ceramide — a central molecule in sphingolipid metabolism — in effect functions as a tumour-suppressor lipid, inducing antiproliferative and apoptotic responses in various cancer cells. Conversely, S1P induces responses that, on aggregate, render S1P a tumour-promoting lipid. These discoveries are paving the way for the advancement of anticancer therapies.

摘要翻译： 

具有生物活性的鞘脂在调控癌症发病过程中若干基本生物学事件中发挥关键作用。近期，在理解以神经酰胺及鞘氨醇-1-磷酸（S1P）介导的具有生物活性的鞘脂合成方面取得重大进展，揭示了这些分子在癌症发生与进展中的重要作用。神经酰胺——鞘脂代谢的核心分子——实质上发挥抑癌脂质的功能，可在多种癌细胞中诱导抗增殖及凋亡反应。相反，S1P诱导的反应总体使其成为促癌脂质。这些发现正为抗癌治疗的进展铺平道路。

原文链接：

Biologically active sphingolipids in cancer pathogenesis and treatment