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Aguilar 2019 Cell Rep
Additional label Labels  + , 2019-11  +
Coupling states LEAK  + , OXPHOS  +
Diseases Cancer  +
Enzyme Uncoupling protein  +
Has abstract Colorectal cancer (CRC) is associated with
Colorectal cancer (CRC) is associated with metabolic and redox perturbation. The mitochondrial transporter uncoupling protein 2 (UCP2) controls cell proliferation ''in vitro'' through the modulation of cellular metabolism, but the underlying mechanism in tumors ''in vivo'' remains unexplored. Using murine intestinal cancer models and CRC patient samples, we find higher UCP2 protein levels in tumors compared to their non-tumoral counterparts. We reveal the tumor-suppressive role of UCP2 as its deletion enhances colon and small intestinal tumorigenesis in AOM/DSS-treated and Apc<sup>Min/+</sup> mice, respectively, and correlates with poor survival in the latter model. Mechanistically, UCP2 loss increases levels of oxidized glutathione and proteins in tumors. UCP2 deficiency alters glycolytic pathways while promoting phospholipid synthesis, thereby limiting the availability of NADPH for buffering oxidative stress. We show that UCP2 loss renders colon cells more prone to malignant transformation through metabolic reprogramming and perturbation of redox homeostasis and could favor worse outcomes in CRC. <small>Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.</small>
er Inc. All rights reserved.</small>  +
Has editor [[Plangger M]]  +
Has info [ PMID: 31461648 Open Access]  +
Has publicationkeywords Colorectal cancer  + , Lipid synthesis  + , Mitochondria  + , Mitochondrial carrier  + , Oxidative stress  + , Tumor metabolic reprogramming  + , Tumor metabolism  + , Uncoupling protein 2  +
Has title Aguilar E, Esteves P, Sancerni T, Lenoir V
Aguilar E, Esteves P, Sancerni T, Lenoir V, Aparicio T, Bouillaud F, Dentin R, Prip-Buus C, Ricquier D, Pecqueur C, Guilmeau S, Alves-Guerra MC (2019) UCP2 deficiency increases colon tumorigenesis by promoting lipid synthesis and depleting NADPH for antioxidant defenses. Cell Rep 28:2306-16.
antioxidant defenses. Cell Rep 28:2306-16.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Genetic knockout;overexpression  +
Pathways N  +
Preparation Homogenate  +
Tissue and cell Endothelial;epithelial;mesothelial cell  +
Was published by MiPNetLab FR Paris Bouillaud F +
Was published in journal Cell Rep +
Was published in year 2019  +
Was written by Aguilar E + , Esteves P + , Sancerni T + , Lenoir V + , Aparicio T + , Bouillaud F + , Dentin R + , Prip-Buus C + , Ricquier D + , Pecqueur C + , Guilmeau S + , Alves-Guerra MC +
Categories Publications
Modification date
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12:59:11, 11 November 2019  +
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