How Do Gangliosides Regulate RTKs Signaling?

Abstract

Gangliosides, the glycosphingolipids carrying one or several sialic acid residues, are located on the outer leaflet of the plasma membrane in glycolipid-enriched microdomains, where they interact with molecules of signal transduction pathways including receptors tyrosine kinases (RTKs). The role of gangliosides in the regulation of signal transduction has been reported in many cases and in a large number of cell types. In this review, we summarize the current knowledge on the biosynthesis of gangliosides and the mechanism by which they regulate RTKs signaling.

Glycosylation in cancer: mechanisms and clinical implications

“…Gangliosides are also overexpressed in tumours such as melanoma, neuroblastoma and breast cancer, in which they mediate cell proliferation, tumour growth and cancer cell migration 17,53 .…”

“…The process of tumour growth and proliferation is characterized by altered glycosylation of key growth factors receptors, which modulates their activity and signalling 161 . Expression of gangliosides in the cancer cell membrane can also modulate signal transduction, activating various cellular pathways that induce tumour growth and progression 17 . Altered O-GlcNAcylation is also associated with cancer progression 153 .…”

“…In vertebrate glycosphingolipids, the glucose moiety is typically substituted with β-linked galactose, creating a lactosylceramide (d-galactosyl-1,4-β-dglucosylceramide). Glycosphingolipids include a series of neutral 'core' structures and gangliosides, which typically carry one or several sialic acids and have been shown to regulate receptor tyrosine kinase (RTK) signalling 17 .…”

High Levels of Anti-Ganglioside Antibodies in Patients with Parkinson?s Disease Associated with Cognitive Decline

“…Specifically, they either inhibit the dimerization and autophosphorylation of the receptors induced by specific ligands, or activate receptors signaling without ligand binding. Moreover, the activation or inhibition of RTKs is dependent on the glycan structure of gangliosides and cellular [12,30]. (b) Moreover, gangliosides have also receptorproperties for viruses and bacterial [12,31].…”

Gangliosides and Antigangliosides in Malignant Melanoma

“…Gangliosides control cell differentiation and proliferation [62][63][64]. Monosialogangliosides suppress cell growth (GM1-MMP9, GM1-PDGF, GM1-NGF, GM3-EGF, GM3-IGFs, GM2-pFAK), while polisialogangliosides stimulate cell growth (GD3 binding integrin, p-FAK, pp130Cas, p=paxilin, p-Yes or GD2 binding p-FAK, p-p38, c-Met) [65].…”