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PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism 期刊论文

编号：

c1598e7b-5cae-42d3-8262-f645a87eb4c5
作者：

Li, Changfeng(李长锋)#*^[1]Zhang, Ying(张莹)^[1]Cheng, Xing^[1];Yuan, Hua^[2];Zhu, Shan(朱珊)^[3]Liu, Jiao^[3]Wen, Qirong^[3];Xie, Yangchun(谢阳春)^[4]Liu, Jinbao(刘金保)^[3]Kroemer, Guido^{[5,6,7,8,9,10,11]}Klionsky, Daniel J.^[12,13]Lotze, Michael T.^[4]Zeh, Herbert J.^[4]Kang, Rui^[4]Tang, Daolin(唐道林)*^[3,4]
语种：

英文
期刊：

DEVELOPMENTAL CELL ISSN：1534-5807 2018 年 46 卷 4 期 (441 - +) ; AUG 20
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摘要：

Pancreatic cancer is an aggressive malignancy with changes in the tumor microenvironment. Here, we demonstrate that PINK1 and PARK2 suppressed pancreatic tumorigenesis through control of mitochondrial iron-dependent immunometabolism. Using mouse models of spontaneous pancreatic cancer, we show that depletion of Pink1 and Park2 accelerates mutant Kras-driven pancreatic tumorigenesis. PINK1-PARK2 pathway-mediated degradation of SLC25A37 and SLC25A28 increases mitochondrial iron accumulation, which leads to the HIF1A-dependent Warburg effect and AIM2-dependent inflammasome activation in tumor cells. AIM2-mediatedHMGB1 release further induces expression of CD274/PD-L1. Consequently, pharmacological administration of mitochondrial iron chelator, anti-HMGB1 antibody, or genetic depletion of Hif1a or Aim2 in pink1(-/-)and park2(-/-)mice confers protection against pancreatic tumorigenesis. Low PARK2 expression and high SLC25A37 and AIM2 expression are associated with poor prognosis in patients with pancreatic cancer. These findings suggest that disrupted mitochondrial iron homeostasis may contribute to cancer development and hence constitute a target for therapeutic intervention.
推荐引用方式
GB/T 7714：

Li Changfeng,Zhang Ying,Cheng Xing, et al. PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism [J].DEVELOPMENTAL CELL,2018,46(4):441-+.
APA：

Li Changfeng,Zhang Ying,Cheng Xing,Yuan Hua,&Tang Daolin.(2018).PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism .DEVELOPMENTAL CELL,46(4):441-+.
MLA：

Li Changfeng, et al. "PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism" .DEVELOPMENTAL CELL 46,4(2018):441-+.
入库时间：

12/4/2019 7:16:54 PM
更新时间：

12/4/2019 7:16:54 PM
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