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Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution
Biomolecules, Volume: 11, Issue: 10, Start page: 1418
Swansea University Author:
Paul Facey
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Copyright: © 2021 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
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DOI (Published version): 10.3390/biom11101418
Abstract
Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for...
| Published in: | Biomolecules |
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| ISSN: | 2218-273X |
| Published: |
MDPI AG
2021
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa58145 |
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| Abstract: |
Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically. |
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| Keywords: |
oncogenesis; methylation; tumorigenesis; drug resistance; cancer stem cell; Warburg effect; transcription factors; NAD+ |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Issue: |
10 |
| Start Page: |
1418 |