Role and Function of O-GlcNAcylation in Cancer

Lee, Jii Bum; Pyo, Kyoung‐Ho; Kim, Hye Ryun

doi:10.3390/cancers13215365

Cited by 59 publications

(38 citation statements)

References 111 publications

(154 reference statements)

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“…O -GlcNAcylation is a key integrator of cellular nutritional status and occurs in the nucleus, cytoplasm, and mitochondrion. It participates in the process of nutrient sensing and metabolism and plays crucial roles in physiology and physiopathology [ 233 , 234 ].…”

Section: Mitochondria Function In Epigenetic Regulationmentioning

confidence: 99%

An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept.

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Section: Mitochondria Function In Epigenetic Regulationmentioning

confidence: 99%

An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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“…Also, any changes in the intracellular and microenvironmental metabolite pools can have a direct effect on O-GlcNAcylation, of which its substrate UDP-GlcNAc is produced through the hexosamine biosynthetic pathway. As glucose, amino acid, fatty acid and nucleotide metabolism are all linked to this pathway and therefore the synthesis of the substrate, any difference in metabolite levels from these pathways might influence O-GlcNAcylation ( 110 ). This highlights the possibility of a direct role for the microenvironment in the interplay between glycosylation and various cell types of the TME.…”

Section: Glycosylationmentioning

confidence: 99%

Metabolite-derived protein modifications modulating oncogenic signaling

Liu

Vandekeere

et al. 2022

Front. Oncol.

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Malignant growth is defined by multiple aberrant cellular features, including metabolic rewiring, inactivation of tumor suppressors and the activation of oncogenes. Even though these features have been described as separate hallmarks, many studies have shown an extensive mutual regulatory relationship amongst them. On one hand, the change in expression or activity of tumor suppressors and oncogenes has extensive direct and indirect effects on cellular metabolism, activating metabolic pathways required for malignant growth. On the other hand, the tumor microenvironment and tumor intrinsic metabolic alterations result in changes in intracellular metabolite levels, which directly modulate the protein modification of oncogenes and tumor suppressors at both epigenetic and post-translational levels. In this mini-review, we summarize the crosstalk between tumor suppressors/oncogenes and metabolism-induced protein modifications at both levels and explore the impact of metabolic (micro)environments in shaping these.

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“…For the past two decades, a growing body of evidence has demonstrated the crucial role of abnormal O -GlcNAcylation of many oncogenes, tumor suppressors, and signaling actors on the growth, adhesion, migration, and invasion of cancer cells. However, while the role of O -GlcNAcylation in carcinogenesis and tumor progression remains of high interest in cancer research ( 24 , 25 ), the impact of this glycosylation in the response of cancer to therapies is poorly investigated. The donor substrate for O -GlcNAcylation UDP-GlcNAc can also be epimerized to uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) or modified into cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac).…”

Section: Introductionmentioning

confidence: 99%

Targeting O-GlcNAcylation to overcome resistance to anti-cancer therapies

Very

Yazidi‐Belkoura

2022

Front. Oncol.

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In cancer cells, metabolic reprogramming is associated with an alteration of the O-GlcNAcylation homeostasis. This post-translational modification (PTM) that attaches O-GlcNAc moiety to intracellular proteins is dynamically and finely regulated by the O-GlcNAc Transferase (OGT) and the O-GlcNAcase (OGA). It is now established that O-GlcNAcylation participates in many features of cancer cells including a high rate of cell growth, invasion, and metastasis but little is known about its impact on the response to therapies. The purpose of this review is to highlight the role of O-GlcNAc protein modification in cancer resistance to therapies. We summarize the current knowledge about the crosstalk between O-GlcNAcylation and molecular mechanisms underlying tumor sensitivity/resistance to targeted therapies, chemotherapies, immunotherapy, and radiotherapy. We also discuss potential benefits and strategies of targeting O-GlcNAcylation to overcome cancer resistance.

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Role and Function of O-GlcNAcylation in Cancer

Cited by 59 publications

References 111 publications

An Epigenetic Role of Mitochondria in Cancer

An Epigenetic Role of Mitochondria in Cancer

Metabolite-derived protein modifications modulating oncogenic signaling

Targeting O-GlcNAcylation to overcome resistance to anti-cancer therapies

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