Abstract
Gangliosides, the glycosphingolipids carrying one or several sialic acid residues, are mostly localized at the plasma membrane in lipid raft domains and implicated in many cellular signaling pathways mostly by interacting with tyrosine kinase receptors. Gangliosides are divided into four series according to the number of sialic acid residues, which can be also modified by O-acetylation. Both ganglioside expression and sialic acid modifications can be modified in pathological conditions such as cancer, which can induce either pro-cancerous or anti-cancerous effects. In this review, we summarize the specific functions of gangliosides in neuro-ectodermal derived tumors, and their roles in reprogramming the lipidomic profile of cell membrane occurring with the induction of epithelial-mesenchymal transition.
Highlights
Gangliosides are acidic glycosphingolipids (GSL) carrying one or more sialic acid residues on their carbohydrate moieties that are mainly located in glycolipid-enriched domains, called lipid rafts, on the outer leaflet of the plasma membrane bilayer
These modified carbohydrate epitopes are defined as tumor associated carbohydrate antigens (TACA), such as GD2 or GD3 ganglioside in neuro-ectodermal derived (ND) cancers [4,5]
We review the changes in ganglioside content that are associated with tumorigenesis, their roles, and the potential therapeutic approaches that target abnormal ganglioside expression
Summary
Gangliosides are acidic glycosphingolipids (GSL) carrying one or more sialic acid residues on their carbohydrate moieties that are mainly located in glycolipid-enriched domains, called lipid rafts, on the outer leaflet of the plasma membrane bilayer. Raft domains are composed of cholesterol, phospholipids, and glycosphingolipids and enriched in specific proteins [1] They engage in major cellular pathways and are involved in cell biological properties under physiological conditions. Irrespective of the elongation status of their core structure (Galβ1-3GalNAcβ1-4Galβ1-4Glcβ1-1Cer), gangliosides are classified in four series (0-, a-, b- and c-series) according to Svennerholm classification [2] in function of the number of sialic acid residues (from 0 to 3) linked to lactosylceramide. Cancer development is generally associated with glycosylation changes of glycolipids and glycoproteins expressed at the cell surface [3] These modified carbohydrate epitopes are defined as tumor associated carbohydrate antigens (TACA), such as GD2 or GD3 ganglioside in neuro-ectodermal derived (ND) cancers [4,5].
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