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Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, 40126 Bologna, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 580;
Received: 29 December 2017 / Revised: 12 February 2018 / Accepted: 14 February 2018 / Published: 15 February 2018
(This article belongs to the Special Issue Glycosylation and Glycoproteins 2017)
Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1) by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2) through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3) by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal. View Full-Text
Keywords: cancer; growth factor receptors; glycosylation; galectins; gangliosides; signal transduction cancer; growth factor receptors; glycosylation; galectins; gangliosides; signal transduction
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Gomes Ferreira, I.; Pucci, M.; Venturi, G.; Malagolini, N.; Chiricolo, M.; Dall’Olio, F. Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling. Int. J. Mol. Sci. 2018, 19, 580.

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