Update on Glycosphingolipids Abundance in Hepatocellular Carcinoma

Abstract

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.

Identification and validation of biomarkers related to lipid metabolism in osteoarthritis based on machine learning algorithms

“…The UGCG gene encodes UDP-glucose ceramide glucosyltransferase, representing the initial crucial step in the biosynthesis of the majority of glycosphingolipids. These lipids play a vital role as components within membrane microstructural domains, facilitating membrane translocation and signal transduction processes [ 33 ]. Naoki Seito et al found that specific knockdown of UGCG in mouse chondrocytes resulted in more severe pathological OA induced by destabilization surgery and similarly more severe cartilage degradation induced by IL-1α in vitro experiments [ 34 ].…”

Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells

“…Simultaneously, gangliosides, a subtype of glycosphingolipids prevalent on cell surfaces, particularly abundant in the nervous tissues of various animals [17], play a pivotal role in cell functions like proliferation, adhesion, migration, and interactions within the cell microenvironment in different cancers [18][19][20][21]. Expression patterns and the underlying mechanisms of gangliosides in normal and cancer cells have been explored by several researchers [22][23][24]. Notably, human melanomas predominantly feature ganglioside GM3 and GD3 on their cell surfaces [25].…”