• Joanne Chia, Germaine Goh, and Frederic Bard.
• Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore.
• Biochim. Biophys. Acta. 2016 Aug 1; 1860 (8): 1623-39.

BackgroundWhile the underlying causes of cancer are genetic modifications, changes in cellular states mediate cancer development. Tumor cells display markedly changed glycosylation states, of which the O-GalNAc glycans called the Tn and TF antigens are particularly common. How these antigens get over-expressed is not clear. The expression levels of glycosylation enzymes fail to explain it.Scope Of ReviewWe describe the regulation of O-GalNAc glycosylation initiation and extension with emphasis on the initiating enzymes ppGalNAcTs (GALNTs), and introduce the GALA pathway--a change in GALNTs compartmentation within the secretory pathway that regulates Tn levels. We discuss the roles of O-GalNAc glycans and GALNTs in tumorigenic processes and finally consider diagnostic and therapeutic perspectives.Major ConclusionsContrary to a common hypothesis, short O-glycans in tumors are not the result of an incomplete glycosylation process but rather reveal the activation of regulatory pathways. Surprisingly, high Tn levels reveal a major shift in the O-glycoproteome rather than a shortening of O-glycans. These changes are driven by membrane trafficking events.General SignificanceMany attempts to use O-glycans for biomarker, antibody and therapeutic vaccine development have been made, but suffer limitations including poor sensitivity and/or specificity that may in part derive from lack of a mechanistic understanding. Deciphering how short O-GalNAc glycans are regulated would open new perspectives to exploit this biology for therapeutic usage. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

26 keywords...

hide…