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

	The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression
刊名	CELL RESEARCH
	2020
卷号	30
关键词	OXIDATIVE STRESS CANCER SULFASALAZINE RADIOTHERAPY PEROXIDATION TRANSPORTER HOMEOSTASIS INHIBITION CHECKPOINT ANTIPORTER
ISSN号	1001-0602
英文摘要	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.
资助项目	[Andrew Sabin Family Fellow Award] ; [Sister Institution Network Fund] ; [Radiation Oncology Strategic Initiatives (ROSI) Platform Seed Grant from The University of Texas MD Anderson Cancer Center] ; [CPRIT Research Training Grant] ; [University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences]
语种	英语
CSCD记录号	CSCD:6706638
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/50568]
专题	中国科学院合肥物质科学研究院
推荐引用方式 GB/T 7714	. The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression[J]. CELL RESEARCH,2020,30.
APA	(2020).The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression.CELL RESEARCH,30.
MLA	"The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression".CELL RESEARCH 30(2020).