Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The β-linked N-acetyl-D-glucosamine (GlcNAc) is a post-translational modification of serine and threonine residues catalyzed by the enzyme O-GlcNAc transferase (OGT). Increased OGT expression is a feature of most human cancers and inhibition of OGT decreases cancer cell proliferation. Anti-proliferative effects are attributed to post-translational modifications of known regulators of cancer cell proliferation, such as MYC, FOXM1 and EZH2. In general, OGT amplifies cell-specific phenotype, for example, OGT overexpression enhances reprogramming efficiency of mouse embryonic fibroblasts into stem cells. Genome-wide screens suggest that certain cancers are particularly dependent on OGT, and understanding these addictions is important when considering OGT as a target for cancer therapy. The O-GlcNAc modification is involved in most cellular processes, which raises concerns of on-target undesirable effects of OGT targeting therapy. Yet, emerging evidence suggest that, much like proteasome inhibitors, specific compounds targeting OGT elicit selective anti-proliferative effects in cancer cells, and can prime malignant cells to other treatments. It is therefore essential to gain mechanistic insights on substrate specificity for OGT, develop reagents to more specifically enrich for O-GlcNAc modified proteins, identify O-GlcNAc 'readers' and develop OGT small molecule inhibitors. Here, we review the relevance of OGT in cancer progression and the potential targeting of this metabolic enzyme as a putative oncogene. Contrasting the functions of any candidate oncogene between normal and cancer cells is rarely done, but only by understanding the normal functions of a given factor, it is possible to understand these functions gone awry. Here we review oncogenic functions of OGT.

Original publication

DOI

10.1158/1541-7786.mcr-20-0926

Type

Journal article

Journal

Molecular cancer research : MCR

Publication Date

20/01/2021

Addresses

Department of Medicine, University of Helsinki h.m.itkonen@gmail.com.