title: Short O-GalNAc glycans: regulation and role in tumor development and clinical perspectives.
abstract: BACKGROUND
  While 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.
  
  
  METHODS
  We 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.
  
  
  CONCLUSIONS
  Contrary 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.
  
  
  CONCLUSIONS
  Many 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.
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore.
authors.forename: Joanne
authors.initials: J
authors.lastname: Chia
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore.
authors.forename: Germaine
authors.initials: G
authors.lastname: Goh
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore; Department of Biochemistry, National University of Singapore, 21 Lower Kent Ridge, Road, 119077, Singapore. Electronic address: fbard@imcb.a-star.edu.sg.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bard
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000235:genetics / Q000378:metabolism; D019496:Cancer Vaccines / Q000627:therapeutic use; D005688:Galactosamine / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009844:Oligosaccharides / Q000235:genetics / Q000378:metabolism
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006023:Glycoproteins; D009363:Neoplasm Proteins; D009844:Oligosaccharides; C040286:Tn antigen; D005688:Galactosamine
keywords: Cancer; GALNTs; Membrane trafficking; O-GalNAc glycosylation