|Title||O-GlcNAc Transferase - An Auxiliary Factor or a Full-blown Oncogene?|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Itkonen HM, Loda M, Mills IG|
|Journal||Mol Cancer Res|
|Date Published||2021 04|
The β-linked N-acetyl-d-glucosamine (GlcNAc) is a posttranslational 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. Antiproliferative effects are attributed to posttranslational 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 antiproliferative 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.
|Alternate Journal||Mol Cancer Res|
|Grant List||CEO13_2-004 / PCUK_ / Prostate Cancer UK / United Kingdom |
R01 CA187918 / CA / NCI NIH HHS / United States
P50 CA211024 / CA / NCI NIH HHS / United States
Massimo Loda, M.D.