Cell子刊:UCP2缺陷促结直肠癌发生
创作:爱的抉择 审核:Lexi 2019年09月09日
  • 小鼠肠癌模型和结直肠癌(CRC)患者样本显示肿瘤中UCP2蛋白水平升高;
  • UCP2敲除促进结直肠癌和小肠癌的发生,与较差的生存率相关;
  • 结直肠癌中UCP2缺失导致抗氧化防御降低、氧化应激水平增加、脂肪酸合成增加、可缓冲氧化应激的NADPH可用性受限;
  • 结直肠癌中UCP2缺失导致代谢相关基因表达改变、糖酵解途径改变,而对氧化代谢和线粒体呼吸没有影响;
  • UCP2缺失导致结直肠细胞代谢重编程和氧化还原平衡失调,从而倾向于恶性转化。
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Lexi
结直肠癌(CRC)与代谢和氧化还原失调有关。线粒体转运体解耦蛋白2(UCP2)在体外通过调控细胞代谢从而控制细胞增殖,而其对体内肿瘤的调控机制尚不明确。发表在Cell Reports上的最新研究发现UCP2通过其缺失使结直肠细胞代谢重编程,且使其氧化还原平衡失调,从而使结直肠细胞倾向于恶性转化。
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Cell Reports [IF:7.815]

UCP2 Deficiency Increases Colon Tumorigenesis by Promoting Lipid Synthesis and Depleting NADPH for Antioxidant Defenses

UCP2缺陷通过促进脂类合成及为抗氧化消耗NADPH从而促进结直肠癌发生

10.1016/j.celrep.2019.07.097

2019-08-27, Article

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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.

First Authors:
Esther Aguilar,Pauline Esteves

Correspondence Authors:
Marie-Clotilde Alves-Guerra

All Authors:
Esther Aguilar,Pauline Esteves,Tiphaine Sancerni,Veronique Lenoir,Thomas Aparicio,Frederic Bouillaud,Renaud Dentin,Carina Prip-Buus,Daniel Ricquier,Claire Pecqueur,Sandra Guilmeau,Marie-Clotilde Alves-Guerra

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