Targeting Hypoxia-Driven Metabolic Reprogramming to Constrain Tumor Progression and Metastasis
Abstract
1. Introduction
2. Biologic Aspects of Tumor Hypoxia
2.1. Acute Hypoxia
2.2. Cyclic Hypoxia
2.3. Chronic Hypoxia
3. Cellular Adaptation to Hypoxia
3.1. Hypoxia-Inducible Factor 1-Alpha (HIF-1α)
3.2. The mTOR Pathway
3.3. UPR
3.4. NF-κB
4. Genetic and Metabolic Modifications in the Hypoxic Tumor Microenvironment
4.1. Promotion of Anaerobic Glycolysis
4.2. Repression of Oxidative Phosphorylation
5. Impact of Metabolic Reprogramming Driven-Hypoxia on Tumor Progression
6. Therapeutic Strategies Targeting Hypoxia
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
4E-BP1 | Eukaryotic initiation factor 4E binding protein 1 |
ALDA | Aldolase A |
AMPK | AMP-activated protein kinase |
ARNT | Aryl hydrocarbon receptor nuclear translocator |
ATF4 | Activating transcription factor 4 |
ATF6 | Activating transcription factor 6 |
BiP | Immunoglobulin protein |
BNIP3 | Bcl2/adenovirus E1B 19-kDa protein-interacting protein 3 |
CA-IX | Carbonic anhydrase IX |
CA-XII | Carbonic anhydrase XII |
COX4-2 | Cytochrome oxidase 4-2 |
CSCs | Cancer stem cells |
CTLs | Cytotoxic T lymphocytes |
DCs | Dendritic cells |
Deptor | DEP-domain-containing mTOR-interacting protein |
DLK1 | Delta-like 1 Homologue |
DNA-PKcs | DNA-dependent protein kinase, catalytic subunit |
ECM | Extracellular matrix |
EEF2K | Eukaryotic elongation factor 2 kinase |
EIF2α | Eukaryotic initiation factor 2 alpha |
EMT | Epithelial to mesenchymal transition |
ENG | Endoglin |
EphA2 | Ephrin type-A receptor 2 |
ER | Endoplasmic reticulum |
F6P | Fructose 6-phosphate |
FBW7 | F-box and WD repeat domain-containing 7 |
FDP | Fructose 1,6-bisphosphate |
G6P | Glucose 6-phosphate |
GLUTs | Glucose transporters |
HA | Hyaluronic acid |
HDAC | Histone deacetylases |
HK2 | Hexokinase 2 |
HIFs | Hypoxia-inducible factors |
HREs | Hypoxia response elements |
IGF2 | Insulin-like growth factor |
IKK | IκB kinase complex |
IL-8 | Interleukin 8 |
IRE1 | Inositol-requiring protein 1 |
LDHA | Lactic dehydrogenase A |
LEP | Leptin |
LRP1 | Low-density lipoprotein receptor-related protein 1 |
MCT1 | Monocarboxylate transporter 1 |
mLST8 | Mammalian lethal with Sec13 protein 8 |
mTOR | Mammalian target of rapamycin |
MXI1 | MAX interactor-1 |
NAD+ | Nicotinamide adenine dinucleotide |
NF-κB | Nuclear factor-κB |
ODDD | Oxygen-dependent degradation domain |
OXPHOS | Oxidative phosphorylation |
p70S6K | P70S6 kinase |
PDGF | Platelet-derived growth factor |
PDH | Pyruvate dehydrogenase |
PDK1 | Pyruvate dehydrogenase kinase |
PERK | Protein kinase RNA-like ER kinase |
PFK1 | Phosphofructokinase 1 |
PFKFB3 | 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 |
PGK1 | Phosphoglycerate kinase 1 |
PIKKs | Phosphatidylinositol 3-kinase-related kinases |
PKM | Pyruvate kinase M |
PML | Promyelocytic leukemia protein |
POU5F1 | POU domain, class 5, transcription factor 1 |
PRAS40 | Proline-rich AKT substrate 40 kDa |
Raptor | Regulatory-associated protein of mTOR |
REDD1 | Regulated in development and DNA damage responses 1 |
ROS | Reactive oxygen species |
TAD | Transactivation domains |
TCA | Tricarboxylic acid cycle |
TAMs | Tumor-associated macrophages |
TFAM | Transcription factor A, mitochondrial |
TGF | Transforming growth factor |
TRAF6 | Tumor necrosis factor receptor associated factor 6 |
Tregs | T cells regulatory |
UPR | Uunfolded protein response |
VEGF-A | Vascular endothelial growth factor-A |
VHL | Von Hippel-Lindau |
XBP1 | X-box binding protein |
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Miranda-Galvis, M.; Teng, Y. Targeting Hypoxia-Driven Metabolic Reprogramming to Constrain Tumor Progression and Metastasis. Int. J. Mol. Sci. 2020, 21, 5487. https://doi.org/10.3390/ijms21155487
Miranda-Galvis M, Teng Y. Targeting Hypoxia-Driven Metabolic Reprogramming to Constrain Tumor Progression and Metastasis. International Journal of Molecular Sciences. 2020; 21(15):5487. https://doi.org/10.3390/ijms21155487
Chicago/Turabian StyleMiranda-Galvis, Marisol, and Yong Teng. 2020. "Targeting Hypoxia-Driven Metabolic Reprogramming to Constrain Tumor Progression and Metastasis" International Journal of Molecular Sciences 21, no. 15: 5487. https://doi.org/10.3390/ijms21155487
APA StyleMiranda-Galvis, M., & Teng, Y. (2020). Targeting Hypoxia-Driven Metabolic Reprogramming to Constrain Tumor Progression and Metastasis. International Journal of Molecular Sciences, 21(15), 5487. https://doi.org/10.3390/ijms21155487