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

查看全文 作　　者：Guang [1,2,3]Lei;Yilei [2]Zhang;Pranavi [2,4]Koppula;Xiaoguang [2]Liu;Jie [2]Zhang;Steven [2,5]HLin;Jaffer [6]AAjani;Qin [1,3]Xiao;Zhongxing [5]Liao;Hui [1,3]Wang;Boyi [2,4]Gan

机构地区：[1]Department of Radiation Oncology,Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School Of Medicine,Central South University,Changsha,Hunan 410013,China;[2]Department of Experimental Radiation Oncology,The University of Texas MD Anderson Cancer Center,Houston,TX 77030,USA;[3]Key Laboratory of Translational Radiation Oncology,Hunan Province,Changsha,Hunan 410013,China;[4]The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences,Houston,TX 77030,USA;[5]Department of Radiation Oncology,Division of Radiation Oncology,The University of Texas MD Anderson Cencer Center,Houston,TX 77030,USA;[6]Department of Gastrointestinal Medical Oncology,Division of Cancer Medicine,The University of Texas MD Anderson Cancer Center,Houston,TX 77030,USA

出　　处：《Cell Research》索引2020年第30卷第2期,共17页

基　　金：Supported by the Andrew Sabin Family Fellow Award,the Sister Institution Network Fund,and a Radiation Oncology Strategic Initiatives(ROSI)Platform Seed Grant from The University of Texas MD Anderson Cancer Center(to B.G.).B.G.is an Andrew Sabin Family Fellow.V.Z.and P.K.were Scholars at the Center for Cancer Epigenetics at The University of Texas MD Anderson Cancer Center.P.K.is also supported by CPRIT Research Training Grant(RP170067);Dr.John.J.Kopchick Research Award from The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences. 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 deficiencyinduced 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. 关键词：PEROXIDATION METABOLISM RADIOTHERAPY

相关文献

参考文献（53）
引证文献（163）
耦合文献（138）

参考文献(53)

引证文献(163)

耦合文献(138)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

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

参考文献(53)

引证文献(163)

耦合文献(138)

用户提示