Abstract
Sphingolipids (SLs) are sphingoid base-containing lipids, which are enriched in plasma membrane microdomains. Some SLs behave as bioactive molecules, modulating cell signalling in various pathophysiological contexts. Whereas ceramide triggers apoptosis and impairs cell migration, sphingosine-1-phosphate (S1P) induces the opposite effects. CD95/Fas, TRAIL-R1 (DR4), and TRAIL-R2 (DR5) are death receptors (DRs) and members of the TNF-R1 superfamily. DRs trigger apoptosis of various cell types, including cancer cells. Over the last two decades, a growing body of evidence indicates that SLs modulate DR signalling. DR stimulation triggers the generation of SLs, including ceramide, sphingosine, and gangliosides. Ceramide has been reported to facilitate DR clustering into lipid rafts upon pro-apoptotic DR agonists. Moreover, ceramide and its metabolites likely contribute to the mitochondrial route of apoptosis. More recently, SLs have been shown to modulate CD95-mediated cell migration of triple negative breast cancer cell lines and Th17 lymphoid cells in response to a nonapoptotic form of CD95L. Herein, we review the role of SLs in DR signalling, including apoptotic and migration pathways.
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Acknowledgements
This work was supported by Ligue nationale contre le cancer, Institut National du Cancer (INCa), INSERM and Paul Sabatier University (Toulouse III). FB is a recipient of a grant from Association de Spécialisation et d’Orientation Scientifique.
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Bilal, F. et al. (2017). Role of Sphingolipids in Death Receptor Signalling. In: Micheau, O. (eds) TRAIL, Fas Ligand, TNF and TLR3 in Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-56805-8_10
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