Ferroptosis regulates key signaling pathways in gastrointestinal tumors:Underlying mechanisms and therapeutic strategies  

作　　者：Ravichandiran Rabitha Sethuraman Shivani Yahya Showket Ganapasam Sudhandiran 

机构地区：[1]Department of Biochemistry,University of Madras,Cell Biology Research Laboratory,Chennai 600025,Tamil Nadu,India

出　　处：《World Journal of Gastroenterology》2023年第16期2433-2451,共19页世界胃肠病学杂志（英文版）

摘　　要：Ferroptosis is an emerging novel form of non-apoptotic,regulated cell death that is heavily dependent on iron and characterized by rupture in plasma membrane.Ferroptosis is distinct from other regulated cell death modalities at the biochemical,morphological,and molecular levels.The ferroptotic signature includes high membrane density,cytoplasmic swelling,condensed mitochondrial membrane,and outer mitochondrial rupture with associated features of accumulation of reactive oxygen species and lipid peroxidation.The selenoenzyme glutathione peroxidase 4,a key regulator of ferroptosis,greatly reduces the lipid overload and protects the cell membrane against oxidative damage.Ferroptosis exerts a momentous role in regulating cancer signaling pathways and serves as a therapeutic target in cancers.Dysregulated ferroptosis orchestrates gastrointestinal(GI)cancer signaling pathways leading to GI tumors such as colonic cancer,pancreatic cancer,and hepatocellular carcinoma.Crosstalk exists between ferroptosis and other cell death modalities.While apoptosis and autophagy play a detrimental role in tumor progression,depending upon the factors associated with tumor microenvironment,ferroptosis plays a decisive role in either promoting tumor growth or suppressing it.Several transcription factors,such as TP53,activating transcription factors 3 and 4,are involved in influencing ferroptosis.Importantly,several molecular mediators of ferroptosis,such as p53,nuclear factor erythroid 2–related factor 2/heme oxygenase-1,hypoxia inducible factor 1,and sirtuins,coordinate with ferroptosis in GI cancers.In this review,we elaborated on key molecular mechanisms of ferroptosis and the signaling pathways that connect ferroptosis to GI tumors.

关 键 词：Ferroptosis Gastrointestinal cancers Nuclear factor erythroid 2-related factor 2 APOPTOSIS AUTOPHAGY 

分 类 号：R735[医药卫生—肿瘤]