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