Redox Biology (Jan 2019)

Enhanced mitochondrial pyruvate transport elicits a robust ROS production to sensitize the antitumor efficacy of interferon-γ in colon cancer

  • YunYan Tai,
  • Fengjun Cao,
  • Mingxing Li,
  • Pindong Li,
  • Tao Xu,
  • Xuanbin Wang,
  • Yuandong Yu,
  • Bing Gu,
  • Xiongjie Yu,
  • Xiaojun Cai,
  • Feng Ao,
  • Peng Ge,
  • Longchao Xiang,
  • Bingbing Yang,
  • Yingpin Jiang,
  • Yong Li

Journal volume & issue
Vol. 20
pp. 451 – 457

Abstract

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Metabolic reprogramming is a feature of cancer cells and crucial for tumor growth and metastasis. Interferon-γ (IFNγ) is a cytokine that plays a pivotal role in host antitumor immunity. However, little is known about the roles of metabolic reprogramming in immune responses. Here, we show that colon cancer cells reprogram metabolism to coordinate proper cellular responses to IFNγ by downregulating mitochondrial pyruvate carrier (MPC)1 and 2 via STAT3 signaling. Forced overexpression of MPC promote the production of reactive oxygen species and enhance the apoptosis induced by IFNγ in colon cancer cells. Moreover, inhibiting STAT3 sensitize the antitumor efficacy of IFN-γ against colon cancer cells. Our findings present a previously unrecognized mechanism that colon cancer manipulate to resist IFNγ mediated antitumor immunity that have implications for targeting a unique aspect of this disease. Keywords: Interferon-γ, Mitochondrial pyruvate carriers, Redox, Colon cancer, Glycolysis