Open Access

The potential role of O-GlcNAc modification in cancer epigenetics

  • Ewa Forma1,
  • Paweł Jóźwiak1,
  • Magdalena Bryś1 and
  • Anna Krześlak1Email author
Cellular & Molecular Biology LettersAn International Journal201419:204

Received: 12 March 2014

Accepted: 1 August 2014

Published: 20 August 2014


There is no doubt that cancer is not only a genetic disease but that it can also occur due to epigenetic abnormalities. Diet and environmental factors can alter the scope of epigenetic regulation. The results of recent studies suggest that O-GlcNAcylation, which involves the addition of N-acetylglucosamine on the serine or threonine residues of proteins, may play a key role in the regulation of the epigenome in response to the metabolic status of the cell. Two enzymes are responsible for cyclic O-GlcNAcylation: O-GlcNAc transferase (OGT), which catalyzes the addition of the GlcNAc moiety to target proteins; and O-GlcNAcase (OGA), which removes the sugar moiety from proteins. Aberrant expression of O-GlcNAc cycling enzymes, especially OGT, has been found in all studied human cancers. OGT can link the cellular metabolic state and the epigenetic status of cancer cells by interacting with and modifying many epigenetic factors, such as HCF-1, TET, mSin3A, HDAC, and BAP1. A growing body of evidence from animal model systems also suggests an important role for OGT in polycomb-dependent repression of genes activity. Moreover, O-GlcNAcylation may be a part of the histone code: O-GlcNAc residues are found on all core histones.


O-GlcNAcylation Cancer O-GlcNAc transferase Histone modifications Host cell factor 1 Ten-eleven translocation Polycomb