School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Theodor Stern-Kai 7, 60590 Frankfurt, Germany.
Int J Mol Sci. 2022 Apr 19;23(9):4477. doi: 10.3390/ijms23094477.
Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer. Low numbers of HCC patients being suitable for liver resection or transplantation and multidrug resistance development during pharmacotherapy leads to high death rates for HCC patients. Understanding the molecular mechanisms of HCC etiology may contribute to the development of novel therapeutic strategies for prevention and treatment of HCC. UDP-glucose ceramide glycosyltransferase (UGCG), a key enzyme in glycosphingolipid metabolism, generates glucosylceramide (GlcCer), which is the precursor for all glycosphingolipids (GSLs). Since UGCG gene expression is altered in 0.8% of HCC tumors, GSLs may play a role in cellular processes in liver cancer cells. Here, we discuss the current literature about GSLs and their abundance in normal liver cells, Gaucher disease and HCC. Furthermore, we review the involvement of UGCG/GlcCer in multidrug resistance development, globosides as a potential prognostic marker for HCC, gangliosides as a potential liver cancer stem cell marker, and the role of sulfatides in tumor metastasis. Only a limited number of molecular mechanisms executed by GSLs in HCC are known, which we summarize here briefly. Overall, the role GSLs play in HCC progression and their ability to serve as biomarkers or prognostic indicators for HCC, requires further investigation.
肝细胞癌 (HCC) 是最常见的原发性肝癌类型。适合肝切除术或肝移植的 HCC 患者数量较少,且药物治疗过程中多药耐药的发展导致 HCC 患者死亡率较高。了解 HCC 病因的分子机制可能有助于开发预防和治疗 HCC 的新治疗策略。UDP-葡萄糖神经酰胺糖基转移酶 (UGCG) 是糖脂代谢中的关键酶,可生成葡萄糖神经酰胺 (GlcCer),这是所有糖脂 (GSL) 的前体。由于 UGCG 基因表达在 0.8%的 HCC 肿瘤中发生改变,因此 GSL 可能在肝癌细胞的细胞过程中发挥作用。在这里,我们讨论了关于 GSL 及其在正常肝细胞、戈谢病和 HCC 中的丰度的现有文献。此外,我们还回顾了 UGCG/GlcCer 在多药耐药发展中的作用、作为 HCC 潜在预后标志物的神经节苷脂、作为潜在肝癌干细胞标志物的神经节苷脂,以及硫酸脑苷脂在肿瘤转移中的作用。目前已知 GSL 在 HCC 中执行的分子机制数量有限,我们在这里简要总结一下。总的来说,GSL 在 HCC 进展中的作用及其作为 HCC 生物标志物或预后指标的能力需要进一步研究。