UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control
Abstract
:1. Introduction
2. Role of UCP2 in the Physiological and Pathophysiological Context
2.1. Biochemical Function
2.1.1. Uncoupling?
2.1.2. Transport of Metabolites
2.2. UCP2 a Metabolic Regulator
2.3. UCP2 and Oxidative Stress: A Link toward Immunity
2.3.1. Insulin Regulation—Type 2 Diabetes (T2D)—Cardiovascular Diseases
2.3.2. Infectious Diseases
2.3.3. Autoimmune Diseases
3. UCP2 and Cancer
3.1. UCP2: A Double-Edged Fight against ROS
3.2. UCP2 and Tumoral Metabolic Reprogramming
3.2.1. Glycolysis
3.2.2. Glutaminolysis
3.2.3. Ca2+ Signaling
3.3. UCP2-Activated Antitumor Immunity
3.4. Drug Sensitivity and Therapeutic Improvement
3.4.1. Genipin
3.4.2. Rosiglitazone
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Disease | Experimental Model | UCP2 Status | Impact | Ref. |
---|---|---|---|---|
Type 2 diabetes | ob/ob mice | Ucp2−/− | Increased glucose-stimulated insulin secretion | [42] |
Ucp2 siRNA | Oxidative stress imbalance | [91,92,93] | ||
Atherosclerosis | Atherogenic diet Ldlr-/-mice | Ucp2−/− Bone marrow | Increased atherosclerotic lesions Increased invasion of macrophages into the intima Oxidative burst | [30] |
Infections | Toxoplasma gondii | Ucp2−/− | Resistance to infection by increased production of ROS and pro- inflammatory molecules | [27] |
Listeria | Ucp2−/− | [28] | ||
Leishmaniasis | Ucp2−/− Ucp2 shRNA | [100,101] | ||
Autoimmune diseases | Streptozotocin (type 1 diabetes) | Ucp2−/− | Higher disease scores Increased oxidative stress and inflammation | [29] |
Experimental autoimmune encephalomyelitis | [54,106,107] | |||
Cancer | Oxidative stress: | |||
AOM/AOM-DSS / APCmin (colorectal cancer) | Ucp2−/− | Decreased protection against oxidative stress and increased colorectal tumorigenesis | [32,108] | |
A549 cell line (lung cancer) | UCP2 overexpression | Reduction of ROS accumulation conferring anti-apoptotic properties | [109] | |
A549 and PaCa44 cell line (lung and pancreatic cancer) | Ucp2 siRNA | ROS stimulate apoptosis derived from autophagy | [109,110] | |
Glycolysis: | ||||
B16F10 cell line (melanoma) | UCP2 overexpression | Less tumorigenic cells through down-regulation of glycolytic enzymes | [111] | |
HuCCT1, TFK-1 and PaCa44 cell lines (bile duct and pancreatic cancer) | Ucp2 siRNA | AMPK activation decreases glycolytic activity and therefore the cell invasiveness | [112,113] | |
Glutaminolysis: | ||||
HPB-ALL cell line (leukemia) | Ucp2 CRISPR | Reduction of oxygen consumption Shift of metabolism to glycolysis Low nucleotide synthesis Decreased cell proliferation | [114] | |
Patu8988T, Panc1 and BxPC3 cell lines (pancreatic cancer) | Ucp2 shRNA | [34] | ||
Ca2+ signaling: | ||||
JB6 P+ and HeLa cell lines (skin and cervix cancer) | UCP2 overexpression | Increased calcium activity stimulates ATP production Long-term mitochondrial dysfunction | [115,116] | |
Immune response: | ||||
Xenografts in mice with B16-OVA and YUMM1 cell lines (melanoma) | UCP2 overexpression | Better prognosis Infiltration of CD8+ T cells and cDC1 cells Improved response to immunotherapy | [117] |
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Luby, A.; Alves-Guerra, M.-C. UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control. Int. J. Mol. Sci. 2022, 23, 15077. https://doi.org/10.3390/ijms232315077
Luby A, Alves-Guerra M-C. UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control. International Journal of Molecular Sciences. 2022; 23(23):15077. https://doi.org/10.3390/ijms232315077
Chicago/Turabian StyleLuby, Angèle, and Marie-Clotilde Alves-Guerra. 2022. "UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control" International Journal of Molecular Sciences 23, no. 23: 15077. https://doi.org/10.3390/ijms232315077