Aguilar 2019 Cell Rep

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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.

» PMID: 31461648 Open Access

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) Cell Rep

Abstract: 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 ApcMin/+ 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.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: Colorectal cancer, Lipid synthesis, Mitochondria, Mitochondrial carrier, Oxidative stress, Tumor metabolic reprogramming, Tumor metabolism, Uncoupling protein 2 Bioblast editor: Plangger M O2k-Network Lab: FR Paris Bouillaud F


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Cancer 

Organism: Mouse  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Homogenate  Enzyme: Uncoupling protein 

Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k 

Labels, 2019-11