Metabolic Adaptation-Mediated Cancer Survival and Progression in Oxidative Stress
Yongquan Tang,
Zhe Zhang,
Yan Chen,
Siyuan Qin,
Li Zhou,
Wei Gao,
Zhisen Shen
Affiliations
Yongquan Tang
Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
Zhe Zhang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
Yan Chen
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
Siyuan Qin
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
Li Zhou
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
Wei Gao
Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu 610106, China
Zhisen Shen
Department of Otorhinolaryngology and Head and Neck Surgery, The Affiliated Lihuili Hospital, Ningbo University, Ningbo 315040, China
Undue elevation of ROS levels commonly occurs during cancer evolution as a result of various antitumor therapeutics and/or endogenous immune response. Overwhelming ROS levels induced cancer cell death through the dysregulation of ROS-sensitive glycolytic enzymes, leading to the catastrophic depression of glycolysis and oxidative phosphorylation (OXPHOS), which are critical for cancer survival and progression. However, cancer cells also adapt to such catastrophic oxidative and metabolic stresses by metabolic reprograming, resulting in cancer residuality, progression, and relapse. This adaptation is highly dependent on NADPH and GSH syntheses for ROS scavenging and the upregulation of lipolysis and glutaminolysis, which fuel tricarboxylic acid cycle-coupled OXPHOS and biosynthesis. The underlying mechanism remains poorly understood, thus presenting a promising field with opportunities to manipulate metabolic adaptations for cancer prevention and therapy. In this review, we provide a summary of the mechanisms of metabolic regulation in the adaptation of cancer cells to oxidative stress and the current understanding of its regulatory role in cancer survival and progression.
