Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer
Abstract
:1. Introduction
2. Cellular Senescence, Circumventing Senescence, and the Onset of Cancer Therapy Resistance
2.1. Dual Roles of Cellular Senescence in Cancer
2.2. Acquisition of Stem Cell Properties in Cancer
2.3. Interwoven Processes of Senescence and EMT—A Major Culprit in Therapy Resistance
3. The Role of NNMT in Acquisition of Stem Cell Properties and Therapy Resistance
3.1. NNMT
3.2. NNMT-Mediated “Nicotinamide Drain” and NAD+ Depletion
3.3. NNMT and Pluripotency
3.4. NNMT and Epigenomic Reprogramming in Cancer
3.5. The Role of NNMT in Acquisition of Metabolic Plasticity and Stem Cell Properties in Cancer
4. ROS and EMT
4.1. Aldehyde Oxidase (AOX1)
The Role of AOX1 in Cancer
5. Concluding Remarks and Open Questions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
2-PY | N1-methyl-2-pyridone-5-carboxamide |
4-PY | N1-methyl-4-pyridone-3-carboxamide |
AADPR | Acetyl Adenosinediphosphate Ribose |
ACMS | Alpha-Amino-Beta-Carboxy-Muconate Semialdehyde |
ACMSD | Alpha-Amino-Beta-Carboxy-Muconate Semialdehyde Decarboxylase |
ADP | Adenosine Diphosphate |
ADPR | Adenosinediphosphate Ribose |
Ahcy | Adenosylhomocysteinase |
AMS | Aminomuconate Semialdehyde |
AOX1 | Aldehyde Oxidase 1 |
APC | Adenomatous Polyposis Coli Protein |
BCL2 | B-cell Lymphoma 2 |
Bhmt | Betaine-Homocysteine Methyltransferase |
BRCA1 | Breast Cancer Type 1 Susceptibility Protein |
cADPR | cyclic Adenosinediphosphate Ribose |
CAF | Cancer Associated Fibroblasts |
CD133 | Cluster of Differentiation 133 |
CD38 | Cluster of Differentiation 38 |
CD44 | Cluster of Differentiation 44 |
CD44s | CD44 standard |
CD44v | CD44 variable |
CDH1 | E-Cadherin |
CDKN2A | Cyclin-Dependent Kinase Inhibitor 2A |
CSC | Cancer Stem Cells |
DRD2 | Dopamine Receptor 2 |
EGLN1 | Egl Nine Homolog 1 |
EMT | Epithelial to Mesenchymal Transition |
EMT-TFs | EMT-Inducing Transcription Factors |
ESRP1 | Epithelial Splicing Regulatory Protein 1 |
EZH1 | Enhancer of Zeste 1 |
EZH2 | Enhancer of Zeste 2 |
GAD3 | Probable Aldehyde Oxidase gad-3 |
GSH | Glutathione |
GSK3β | Glycogen Synthase Kinase 3β |
GSSG | Oxidized Glutathione |
hESC | human Embryonic Stem Cells |
HGSC | High Grade Ovarian Serous Carcinoma |
HIF1α | Hypoxia Inducible Factor 1 Alpha |
HNCC | Head and Neck Carcinoma Cells |
HNF1 β | Hepatocyte Nuclear Factor 1β |
IDO | Indoleamine 2,3-dioxygenase |
IL-6 | Interleukin 6 |
iPSC | induced Pluripotent Stem Cells |
LCMT1 | Leucine Carboxyl Methyltransferase 1 |
LCMT1 | Leucine Carboxyl Methyl Transferase 1 |
mAOX1 | mouse Aldehyde Oxidase 1 |
MAPK | Mitogen-Activated Protein Kinase |
Mat1a | Methionine Adenosyltransferase I alpha |
MET | Mesenchymal to Epithelial Transition |
MNAM | 1-Methylnicotinamide |
MOCOS | Molybdenium Cofactor Sulfurase |
NA | Nicotinic acid |
NAAD | Nicotinic Acid Adenine Dinucleotide |
NAD+ | Nicotinamide Adenine Dinucleotide |
NADS | Nicotinamide Adenine Dinucleotide Synthetase |
NAM | Nicotinamide |
NAMN | Nicotinic Acid Mononucleotide |
NAMPT | Nicotinamide Phosphoribosyltransferase |
NAPRT | Nicotinic Acid Phosphoribosyltransferase |
NMN | Nicotinamide Mononucleotide |
NMNAT | Nicotinamide Mononucleotide Adenylyl-Transferase |
NNMT | Nicotinamide N-Methyltransferase |
NR | Nicotinamide Riboside |
NRK | Nicotinamide Riboside Kinase |
NRF1 | NF-E2-Related Factor 1 |
NRF2 | NF-E2-Related Factor 2 |
OXPHOS | Oxidative Phosphorylation |
PARP | Poly [ADP-ribose] Polymerase |
PHD2 | Prolyl Hydroxylase 2 |
PI3K | Phosphatidylinositol 3-Kinase |
PP2A | Protein Phosphatase 2 |
QPRT | Quinolinate Phosphoribosyltransferase |
ROS | Reactive Oxygen Species |
SAM | S-Adenosyl Methionine |
SASP | Senescence-Associated Secretory Phenotype |
SIRT1 | NAD-Dependent Protein Deacetylase Sirtuin-1 |
SNP | Single Nucleotide Polymorphism |
STAT3 | Signal Transducer and Activator of Transcription 3 |
SUV39H1 | Suppressor of Variegation 3-9 Homolog 1 |
TDO | Tryptophan 2,3-dioxygenase |
TGFβ | Transforming Growth Factor-β |
TIS | Therapy-Induced Senescence |
TME | Tumor Microenvironment |
TP53 | Tumor Suppressor p53 |
Trp | Tryptophan |
ZEB1 | Zinc Finger E-box-Binding Homeobox 1 |
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Novak Kujundžić, R.; Prpić, M.; Đaković, N.; Dabelić, N.; Tomljanović, M.; Mojzeš, A.; Fröbe, A.; Trošelj, K.G. Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer. Int. J. Mol. Sci. 2021, 22, 5681. https://doi.org/10.3390/ijms22115681
Novak Kujundžić R, Prpić M, Đaković N, Dabelić N, Tomljanović M, Mojzeš A, Fröbe A, Trošelj KG. Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer. International Journal of Molecular Sciences. 2021; 22(11):5681. https://doi.org/10.3390/ijms22115681
Chicago/Turabian StyleNovak Kujundžić, Renata, Marin Prpić, Nikola Đaković, Nina Dabelić, Marko Tomljanović, Anamarija Mojzeš, Ana Fröbe, and Koraljka Gall Trošelj. 2021. "Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer" International Journal of Molecular Sciences 22, no. 11: 5681. https://doi.org/10.3390/ijms22115681