Gangliosides in Cancer Cell Signaling.

At the outer leaflet of the plasma membrane, gangliosides are found with other glycosphingolipids, phospholipids, and cholesterol in glycolipid-enriched microdomains, in which they interact with signaling molecules including receptor tyrosine kinases and signal transducers. The role of gangliosides in the regulation of signal transduction has been reported for many cases and in different cell types. The biosynthesis of gangliosides involves specific enzymes, mainly glycosyltransferases that control together with glycohydrolases, the steady state of gangliosides at the cell surface. Changes in ganglioside composition are therefore correlated with modifications of glycosyltransferases or glycohydrolases expression and result in the deregulation of cellular signals. In several types of cancers, the overexpression of disialogangliosides, such as GD3 or GD2 mainly results in the activation of cell signaling, increasing cell proliferation and migration, as well as tumor growth. In this chapter, we summarize our current knowledge of ganglioside biosynthesis, degradation, and of their role in cell signaling regulation in cancers.