Gangliosides: The Double-Edge Sword of Neuro-Ectodermal Derived Tumors

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.

Keywords: cancer; epithelial-mesenchymal transition; gangliosides; signal transduction; therapy.

Figure 1

Simplified representation of ganglioside biosynthesis. Gangliosides are classified in four series according to the number of sialic acid residues linked to lactosylceramide (LacCer) [2]. The 0-series gangliosides are directly synthesized from LacCer and the precursors of other series are synthesized by specific sialyltransferases: ST3Gal V (GM3 synthase), ST8Sia I (GD3 synthase) and ST8Sia V (GT3 synthase), respectively. The elongation of precursors is performed by the sequential action of N-acetyl-galactosaminyltransferase (β4GalNAc T1), galactosyltransferase (β3Gal T4) and sialyltransferases (ST3Gal II and ST8Sia V). Cer, ceramide. Adapted from [6].

Figure 2

Interactions of gangliosides with growth factor receptors in neuro-ectodermal derived (ND) cancers. (A) Negative regulation of malignant properties of cancers cells through GM1 and GM3 interaction with growth factor receptor. (B) Positive regulation of malignant properties of neuronal cells through interactions of TrkA receptor with GM1 in the presence of NGF (1) or with GD1b and GT1b in the absence of NGF (2) [53].

Figure 3

GD2- and GD3-associated MAPK signaling activation. (A) GD3-associated c-Met, EGFR and collagen I activation of MAPK signaling. (B) GD2-associated c-Met constitutive activation and integrin activation induce downstream activation of MAPK signaling.