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- Aguilar 2019 Cell Rep + (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.</br></br><small>Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.</small>ors. Published by Elsevier Inc. All rights reserved.</small>)
