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
Affiliations
YunYan Tai
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Fengjun Cao
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Mingxing Li
Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430030, P.R.China
Pindong Li
Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R.China
Tao Xu
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Xuanbin Wang
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China; Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Yuandong Yu
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China; Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R.China
Bing Gu
Department of Oncology, Danjiangkou First Hospital, Danjiangkou, Hubei 442700, P.R.China
Xiongjie Yu
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Xiaojun Cai
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Feng Ao
Department of Medical Imaging Center, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Peng Ge
Department of Medical Imaging Center, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Longchao Xiang
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Bingbing Yang
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Yingpin Jiang
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China
Yong Li
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China; Institute of Cancer Research, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R.China; Corresponding author at: Department of Oncology, Renmin Hospital, Hubei University of Medicine, 39 Chaoyang middle Rd., Shiyan, Hubei 442000, PR China.
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
