Abstract
O-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions. O-acetylation of gangliosides is dependent on sialyl-O-acetyltransferases and sialyl-O-acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl-O-acetyltransferases (SOAT) described until now. O-acetylated ganglioside species are mainly expressed during embryonic development and in the central nervous system in healthy adults, but are re-expressed during cancer development and are considered as markers of cancers of neuroectodermal origin. However, the specific biological roles of O-acetylated gangliosides in developing and malignant tissues have not been extensively studied, mostly because of the requirement of specific approaches and tools for sample preparation and analysis. In this review, we summarize our current knowledge of ganglioside biosynthesis and expression in normal and pathological conditions, of ganglioside O-acetylation analysis and expression in cancers, and of the possible use of O-acetylated gangliosides as targets for cancer immunotherapy.
Highlights
Gangliosides are a sub-class of glycosphingolipids (GSL), defined by the presence of sialic acid residues
We summarize our current knowledge on O-acetylated ganglioside expression patterns and evidence
The expression pattern of O-acetylated gangliosides was studied in melanoma, neuroblastoma and breast cancer cell lines, and allowed to highlight the expression of OAcGM1, OAcGD3, OAcGD2, OAcGT2 and OAcGT3, with O-acetylation occurring mostly on the C9 position of sialic acid residues
Summary
Gangliosides are a sub-class of glycosphingolipids (GSL), defined by the presence of sialic acid residues. The structure of the carbohydrate moiety of gangliosides is based on a tetrasaccharide backbone substituted by up to five sialic acid residues, giving rise to a large number of oligosaccharide structures [1]. These are mostly expressed at the outer leaflet of the plasma membrane of mammalian cells where they interact with phospholipids, cholesterol, and specific transmembrane proteins, forming detergent-resistant microdomains termed “lipid rafts”. Sialic acid residues can be O-acetylated, increasing the structural heterogeneity of the oligosaccharide structures and modulating ganglioside functions. Cells 2020, 9, 741 a potential functional significance of ganglioside O-acetylation in cancer. The use of O-acetylated gangliosides as targets for cancer immunotherapy is discussed
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