南方科技大学知识苑(SUSTech KC): NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway

题名	NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway
作者	Liu，Pengfei 1,2; Wu，Di 3; Duan，Jinyue 3; Xiao，Hexin 3; Zhou，Yulai 3; Zhao，Lei1,2 ; Feng，Yetong 1,2,3
通讯作者	Liu，Pengfei
发表日期	2020-10-01
DOI	10.1016/j.redox.2020.101702
发表期刊	Redox Biology 影响因子和分区
ISSN	2213-2317
卷号	37
摘要	Transcription factor nuclear factor-erythroid 2-like 2 (NRF2) mainly regulates cellular antioxidant response, redox homeostasis and metabolic balance. Our previous study illustrated the translational significance of NRF2-mediated transcriptional repression, and the transcription of FOCAD gene might be negatively regulated by NRF2. However, the detailed mechanism and the related significance remain unclear. In this study, we mainly explored the effect of NRF2-FOCAD signaling pathway on ferroptosis regulation in human non-small-cell lung carcinoma (NSCLC) model. Our results confirmed the negative regulation relationship between NRF2 and FOCAD, which was dependent on NRF2-Replication Protein A1 (RPA1)-Antioxidant Response Elements (ARE) complex. In addition, FOCAD promoted the activity of focal adhesion kinase (FAK), which further enhanced the sensitivity of NSCLC cells to cysteine deprivation-induced ferroptosis via promoting the tricarboxylic acid (TCA) cycle and the activity of Complex I in mitochondrial electron transport chain (ETC). However, FOCAD didn't affect GPX4 inhibition-induced ferroptosis. Moreover, the treatment with the combination of NRF2 inhibitor (brusatol) and erastin showed better therapeutic action against NSCLC in vitro and in vivo than single treatment, and the improved therapeutic function partially depended on the activation of FOCAD-FAK signal. Taken together, our study indicates the close association of NRF2-FOCAD-FAK signaling pathway with cysteine deprivation-induced ferroptosis, and elucidates a novel insight into the ferroptosis-based therapeutic approach for the patients with NSCLC.
关键词	FAK Ferroptosis FOCAD Mitochondria NRF2 NSCLC
相关链接	[Scopus记录]
收录类别	SCI
语种	英语
学校署名	第一 ; 通讯
资助项目	National Natural Science Foundation of China[31900547] ; China Postdoctoral Science Foundation["2019M653277","2020T130250"] ; Shenzhen Peacock Plan[KQTD2016113015442590]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000604989100001
出版者	ELSEVIER
Scopus记录号	2-s2.0-85090198409
来源库	Scopus
引用统计	被引频次[WOS]：82
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/184678
专题	南方科技大学第一附属医院
作者单位	1.Ambulatory Surgical Center,The 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University,The 1st Affiliated Hospitals of Southern University of Science and Technology,Shenzhen,518020,China 2.Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou,510632,China 3.School of Pharmaceutical Sciences,Jilin University,Changchun,130012,China
第一作者单位	南方科技大学第一附属医院
通讯作者单位	南方科技大学第一附属医院
第一作者的第一单位	南方科技大学第一附属医院
推荐引用方式 GB/T 7714	Liu，Pengfei,Wu，Di,Duan，Jinyue,et al. NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway[J]. Redox Biology,2020,37.
APA	Liu，Pengfei.,Wu，Di.,Duan，Jinyue.,Xiao，Hexin.,Zhou，Yulai.,...&Feng，Yetong.(2020).NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway.Redox Biology,37.
MLA	Liu，Pengfei,et al."NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway".Redox Biology 37(2020).