O-GlcNAcylation in Cancer Biology: Linking Metabolism and Signaling

J Mol Biol. 2016 Aug 14;428(16):3282-3294. doi: 10.1016/j.jmb.2016.05.028. Epub 2016 Jun 23.


The hexosamine biosynthetic pathway (HBP) is highly dependent on multiple metabolic nutrients including glucose, glutamine, and acetyl-CoA. Increased flux through HBP leads to elevated post-translational addition of β-D-N-acetylglucosamine sugars to nuclear and cytoplasmic proteins. Increased total O-GlcNAcylation is emerging as a general characteristic of cancer cells, and recent studies suggest that O-GlcNAcylation is a central communicator of nutritional status to control key signaling and metabolic pathways that regulate multiple cancer cell phenotypes. This review summarizes our current understanding of changes of O-GlcNAc cycling enzymes in cancer, the role of O-GlcNAcylation in tumorigenesis, and the current challenges in targeting this pathway therapeutically.

Keywords: O-GlcNAcylation; OGT; cancer; glycosylation; signaling.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biosynthetic Pathways / physiology*
  • Carcinogenesis / pathology*
  • Glycosylation*
  • Humans
  • Metabolic Networks and Pathways / physiology*
  • Neoplasms / pathology*
  • Signal Transduction / physiology