The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression

被引:809
|
作者
Lei, Guang [1 ,2 ,3 ,4 ]
Zhang, Yilei [3 ]
Koppula, Pranavi [3 ,5 ]
Liu, Xiaoguang [3 ]
Zhang, Jie [3 ]
Lin, Steven H. [3 ,6 ]
Ajani, Jaffer A. [7 ]
Xiao, Qin [1 ,2 ,4 ]
Liao, Zhongxing [6 ]
Wang, Hui [1 ,2 ,4 ]
Gan, Boyi [3 ,5 ]
机构
[1] Cent S Univ, Hunan Canc Hosp, Dept Radiat Oncol, Changsha 410013, Hunan, Peoples R China
[2] Cent S Univ, Affiliated Canc Hosp, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China
[3] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA
[4] Key Lab Translat Radiat Oncol, Changsha 410013, Hunan, Peoples R China
[5] Univ Texas MD Anderson Canc Ctr, UTHealth Grad Sch Biomed Sci, Houston, TX 77030 USA
[6] Univ Texas MD Anderson Cenc Ctr, Dept Radiat Oncol, Div Radiat Oncol, Houston, TX 77030 USA
[7] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Div Canc Med, Houston, TX 77030 USA
关键词
OXIDATIVE STRESS; CANCER; SULFASALAZINE; RADIOTHERAPY; PEROXIDATION; TRANSPORTER; HOMEOSTASIS; INHIBITION; CHECKPOINT; ANTIPORTER;
D O I
10.1038/s41422-019-0263-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
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.
引用
收藏
页码:146 / 162
页数:17
相关论文
共 50 条
  • [21] IONIZING RADIATION-INDUCED MUTAGENESIS
    BREIMER, LH
    BRITISH JOURNAL OF CANCER, 1988, 57 (01) : 6 - 18
  • [22] CRITICAL DNA TARGET SIZE MODEL OF IONIZING RADIATION-INDUCED MAMMALIAN-CELL DEATH
    RADFORD, IR
    HODGSON, GS
    MATTHEWS, JP
    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1988, 54 (01) : 63 - 79
  • [23] Gangliosides protect human melanoma cells from ionizing radiation-induced clonogenic cell death
    Thomas, CP
    Buronfosse, A
    Combaret, V
    Pedron, S
    Fertil, B
    Portoukalian, J
    GLYCOCONJUGATE JOURNAL, 1996, 13 (03) : 377 - 384
  • [24] Ionizing radiation-induced mitophagy promotes ferroptosis by increasing intracellular free fatty acids
    Yang, Pengfei
    Li, Jin
    Zhang, Tianyi
    Ren, Yanxian
    Zhang, Qiuning
    Liu, Ruifeng
    Li, Haining
    Hua, Junrui
    Wang, Wen-An
    Wang, Jufang
    Zhou, Heng
    CELL DEATH AND DIFFERENTIATION, 2023, 30 (11): : 2432 - 2445
  • [25] Ionizing radiation-induced mitophagy promotes ferroptosis by increasing intracellular free fatty acids
    Pengfei Yang
    Jin Li
    Tianyi Zhang
    Yanxian Ren
    Qiuning Zhang
    Ruifeng Liu
    Haining Li
    Junrui Hua
    Wen-An Wang
    Jufang Wang
    Heng Zhou
    Cell Death & Differentiation, 2023, 30 : 2432 - 2445
  • [26] Non-canonical mitophagy induced by Mieap and its role in tumor suppression via ferroptosis-like cell death
    Nakamura, Yasuyuki
    Tsuneki, Masayuki
    Yamamoto, Makoto
    Kinjo, Takao
    Futamura, Manabu
    Kuma, Akiko
    Arakawa, Hirofumi
    CANCER SCIENCE, 2018, 109 : 81 - 81
  • [27] Role of caspases in ionizing radiation-induced apoptosis in the developing cerebellum
    Ferrer, I
    JOURNAL OF NEUROBIOLOGY, 1999, 41 (04): : 549 - 558
  • [28] Advances on the Role of Ferroptosis in Ionizing Radiation Response
    Wang, Fang
    Dai, Qinghui
    Xu, Luhan
    Gan, Lu
    Shi, Yidi
    Yang, Mingjun
    Yang, Shuhong
    CURRENT PHARMACEUTICAL BIOTECHNOLOGY, 2024, 25 (04) : 396 - 410
  • [29] Radiation-induced Cell Death and Its Mechanisms
    Jiao, Yunfei
    Cao, Fangyu
    Liu, Hu
    HEALTH PHYSICS, 2022, 123 (05): : 376 - 386
  • [30] DIVISION PROBABILITY AND RADIATION-INDUCED CELL DEATH
    JAMES, AP
    NATURE, 1967, 213 (5078) : 843 - &