Defining the functions and translational potential of ferroptosis

定义铁死亡的功能和转化潜力

• 批准号: 9978733
• 负责人: Brent R Stockwell
• 金额: $ 95.52万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-02 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978733
• 关键词: Automobile Driving; Cell Death; Goals; Lipid Peroxidation; Lipids; Malignant Neoplasms; Nutrient; Oxidative Stress; Pathway interactions; Process; Research; Signal Transduction; Tumor Suppression; experience; glutathione peroxidase; oxidative damage; repair enzyme; repaired; small molecule; tumor

Ferroptosis in a new form of regulated, non-apoptotic cell death that we discovered; we have determined the major mechanisms regulating activation of ferroptosis and several contexts where it can be induced in sensitized tumors. We found that ferroptosis is ultimately characterized by excessive lipid peroxidation upon loss of activity of the lipid repair enzyme glutathione peroxidase 4 (Gpx4). We propose here the hypothesis that lipid peroxidation serves as a signal to detect a scarcity of nutrients needed tor repair of oxidative damage, and that ferroptosis serves as an innate tumor suppression mechanism to eliminate nascent tumors experiencing such oxidative stress. We further propose to elucidate mechanisms driving ferroptosis in specific cancer contexts, and whether it is feasible to create precision small molecule activators of ferroptosis that eliminate tumors that have become addicted to this repair pathway.

我们发现了一种新的调节性、非凋亡性细胞死亡形式的铁下垂；我们 确定了调节铁性下垂活化的主要机制和几个 可以在致敏肿瘤中诱导的环境。我们发现铁性上睑下垂 最终以脂质失去活性时过度的脂质过氧化为特征 谷胱甘肽过氧化物酶4(Gpx4)。我们在这里提出一个假设，即 脂质过氧化是检测修复所需营养缺乏的信号 氧化损伤，铁性下垂是一种先天的肿瘤抑制 消除经历这种氧化应激的新生肿瘤的机制。我们进一步 建议阐明在特定癌症背景下导致铁性下垂的机制，以及 是否有可能制造出精确的铁下垂小分子激活剂 清除那些已经对这种修复途径上瘾的肿瘤。