UCP2 knockout suppresses mouse skin carcinogenesis

Cancer Prevention Research
Wenjuan LiYunfeng Zhao

Abstract

Mitochondrial uncoupling (uncouples electron transport from ATP production) has recently been proposed as a novel survival mechanism for cancer cells, and reduction in free radical generation is the accepted mechanism of action. However, there is no direct evidence supporting that uncoupling proteins promote carcinogenesis. Herein, we examined whether mitochondrial uncoupling affects mouse skin carcinogenesis using uncoupling protein 2 (UCP2) homozygous knockout and wild-type mice. The results indicate that knockout of Ucp2 significantly reduced the formation of both benign (papilloma) and malignant (squamous cell carcinoma) tumors. UCP2 knockout did not cause increases in apoptosis during skin carcinogenesis. The rates of oxygen consumption were decreased only in the carcinogen-treated UCP2 knockout mice, whereas glycolysis was increased only in the carcinogen-treated wild-type mice. Finally, the levels of metabolites pyruvate, malate, and succinate showed different trends after carcinogen treatments between the wild-type and UCP2 knockout mice. Our study is the first to demonstrate that Ucp2 knockout suppresses carcinogenesis in vivo. Together with early studies showing that UCP2 is overexpressed in a number of human cancers,...Continue Reading

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Citations

Aug 28, 2015·Nature Communications·Sara M NowinskiEdward M Mills
Jun 3, 2017·Molecular Carcinogenesis·Annapoorna SreedharYunfeng Zhao
Jan 21, 2018·Antioxidants & Redox Signaling·Petr JežekMartin Jabůrek
Feb 15, 2018·The Journal of International Medical Research·Li-Feng DongYi-Ding Chen
Feb 16, 2019·Frontiers in Cell and Developmental Biology·Oluwaseun B Ogunbona, Steven M Claypool
Nov 23, 2017·Metabolism: Clinical and Experimental·Senta M KapnickPeter J McGuire
Mar 26, 2021·Frontiers in Oncology·Frederic A VallejoRegina M Graham

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