戈谢病与癌症：从鞘脂角度的探讨
Gaucher's disease and cancer: a sphingolipid perspective.
作者信息
Barth Brian M, Shanmugavelandy Sriram S, Tacelosky Diana M, Kester Mark, Morad Samy A F, Cabot Myles C
机构信息
Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA.
出版信息
Crit Rev Oncog. 2013;18(3):221-34. doi: 10.1615/critrevoncog.2013005814.
Gaucher's disease is a sphingolipidosis characterized by a specific deficiency in an acidic glucocerebrosidase, which results in aberrant accumulation of glucosylceramide primarily within the lysosome. Gaucher's disease has been correlated with cases of myeloma, leukemia, glioblastoma, lung cancer, and hepatocellular carcinoma, although the reasons for the correlation are currently being debated. Some suggest that the effects of Gaucher's disease may be linked to cancer, while others implicate the therapies used to treat Gaucher's disease. This debate is not entirely surprising, as the speculations linking Gaucher's disease with cancer fail to address the roles of ceramide and glucosylceramide in cancer biology. In this review, we will discuss, in the context of cancer biology, ceramide metabolism to glucosylceramide, the roles of glucosylceramide in multidrug-resistance, and the role of ceramide as an anticancer lipid. This review should reveal that it is most practical to associate elevated glucosylceramide, which accompanies Gaucher's disease, with the progression of cancer. Furthermore, this review proposes that the therapies used to treat Gaucher's disease, which augment ceramide accumulation, are likely not linked to correlations with cancer.
戈谢病是一种鞘脂贮积病，其特征是酸性葡萄糖脑苷脂酶特异性缺乏，导致葡萄糖神经酰胺主要在溶酶体内异常蓄积。戈谢病已与骨髓瘤、白血病、胶质母细胞瘤、肺癌和肝细胞癌病例相关，尽管目前对于这种相关性的原因仍存在争议。一些人认为戈谢病的影响可能与癌症有关，而另一些人则认为是用于治疗戈谢病的疗法导致的。这场争论并不完全令人意外，因为将戈谢病与癌症联系起来的推测未能阐明神经酰胺和葡萄糖神经酰胺在癌症生物学中的作用。在本综述中，我们将在癌症生物学的背景下讨论神经酰胺代谢为葡萄糖神经酰胺的过程、葡萄糖神经酰胺在多药耐药性中的作用以及神经酰胺作为抗癌脂质的作用。本综述应表明，将戈谢病伴随的葡萄糖神经酰胺升高与癌症进展联系起来是最合理的。此外，本综述提出，用于治疗戈谢病的疗法会增加神经酰胺的蓄积，这可能与癌症相关性并无关联。
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