Gangliosides: Structures, Biosynthesis, Analysis, and Roles in Cancer

Abstract

Gangliosides are acidic glycosphingolipids containing one or more sialic acid residues. They are essential compounds at the outer leaflet of the plasma membrane, where they interact with phospholipids, cholesterol, and transmembrane proteins, forming lipid rafts. They are involved in cell adhesion, proliferation, and recognition processes, as well as in the modulation of signal transduction pathways. These functions are mainly governed by the glycan moiety, and changes in the structures of gangliosides occur under pathological conditions, particularly in neuro‐ectoderm‐derived cancers. With the progress in mass spectrometry analysis of gangliosides, their role in cancer progression can be now investigated in more detail. In this review we summarize the current knowledge on the biosynthesis of gangliosides and their role in cancers, together with the recent development of cancer immunotherapy targeting gangliosides.

Sialic acid and biology of life: An introduction

“…But upregulated expression of sialyltransferases like ST3Gal-I is observed in human BC [354] and upregulated ST6Gal-I is reported in human BC and colon cancer. Ganglioside overexpression in cancer has been reported such as CNS-specific GD3s from tumor tissues [355]. The overexpression of 9-O-acetylated sialic acid in BC [356], childhood ALL [83,[103][104][105][106][107] are reported.…”

Gangliosides in Nerve Cell Specification

“…108–111 In addition, the aberrant and elevated expression of gang-liosides has also been observed in many types of cancer cells, thereby promoting tumor survival. 112,113 Novel epigenetic regulatory mechanisms for GSLs will contribute to a better understanding of the pathway switch observed during neuronal differentiation of NSCs. In addition, epigenetic regulation of GSLs will provide clues underlying the pathogenic mechanisms, which are useful in developing novel strategies for disease treatment and tissue damage repair.…”

O-acetylated Gangliosides as Targets for Cancer Immunotherapy

“…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".…”

“…They are mainly, but not exclusively, derived from ganglio-series GSL (GgCer) that result from the substitution of a ceramide (Cer) by the tetrasaccharide core Galβ1-3GalNAcβ1-4Galβ1-4Glcβ (Gg4). In different cell types and tissues, gangliosides are usually found as a mixture of di-, tri-and tetrasaccharide cores substituted by one or more sialic acid residues [1,5]. The biosynthesis of gangliosides takes place in the Golgi apparatus and starts by the transfer of sialic acid residues to lactosylceramide (LacCer) by specific sialyltransferases, i.e., the CMP-Neu5Ac: LacCer α2,3-sialyltransferase ST3Gal V (GM3 synthase) [6], the CMP-Neu5Ac: GM3 α2,8-sialyltransferase ST8Sia I (GD3 synthase) [7] and the CMP-Neu5Ac: GD3 α2,8-sialyltransferase ST8Sia V [8], that show high specificity toward glycolipid substrates [9].…”