抗辐射性
生物
GPX4
脂质过氧化
程序性细胞死亡
癌细胞
癌症研究
细胞凋亡
癌症
活性氧
细胞生物学
化学
电离辐射
细胞培养
氧化应激
生物化学
超氧化物歧化酶
辐照
遗传学
物理
核物理学
谷胱甘肽过氧化物酶
作者
Guang Lei,Yilei Zhang,Pranavi Koppula,Xiaoguang Liu,Jie Zhang,Steven H. Lin,Jaffer A. Ajani,Qin Xiao,Zhongxing Liao,Hui Wang,Boyi Gan
出处
期刊:Cell Research
[Springer Nature]
日期:2020-01-16
卷期号:30 (2): 146-162
被引量:793
标识
DOI:10.1038/s41422-019-0263-3
摘要
Ferroptosis, a form of regulated cell death caused by lipid peroxidation, was recently identified as a natural tumor suppression mechanism. Here, we show that ionizing radiation (IR) induces ferroptosis in cancer cells. Mechanistically, IR induces not only reactive oxygen species (ROS) but also the expression of ACSL4, a lipid metabolism enzyme required for ferroptosis, resulting in elevated lipid peroxidation and ferroptosis. ACSL4 ablation largely abolishes IR-induced ferroptosis and promotes radioresistance. IR also induces the expression of ferroptosis inhibitors, including SLC7A11 and GPX4, as an adaptive response. IR- or KEAP1 deficiency-induced SLC7A11 expression promotes radioresistance through inhibiting ferroptosis. Inactivating SLC7A11 or GPX4 with ferroptosis inducers (FINs) sensitizes radioresistant cancer cells and xenograft tumors to IR. Furthermore, radiotherapy induces ferroptosis in cancer patients, and increased ferroptosis correlates with better response and longer survival to radiotherapy in cancer patients. Our study reveals a previously unrecognized link between IR and ferroptosis and indicates that further exploration of the combination of radiotherapy and FINs in cancer treatment is warranted.
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