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Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein 期刊论文 WOS高被引论文

编号：

76ab263e-b9fe-4c09-b48d-b151439c516e
作者：

Dai, Enyong(代恩勇)#^[1]Han, Leng(韩冷)^[1]Liu, Jiao^[2];Xie, Yangchun^[3];Kroemer, Guido^[4,5,6,7,8];Klionsky, Daniel J.^[9,10];Zeh, Herbert J.^[11];Kang, Rui^[11];Wang, Jing(王静)*^[12]Tang, Daolin(唐道林)*^[2,11]
语种：

英文
期刊：

AUTOPHAGY ISSN：1554-8627 2020 年 16 卷 11 期 (2069 - 2083) ; NOV 1
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关键词：

KRAS macrophage DAMP autophagy ferroptosis exosomes
摘要：

KRAS is the most frequently mutated oncogene in human neoplasia. Despite a large investment to understand the effects of KRAS mutation in cancer cells, the direct effects of the oncogenetic KRAS activation on immune cells remain elusive. Here, we report that extracellular KRAS(G12D) is essential for pancreatic tumor-associated macrophage polarization. Oxidative stress induces KRAS(G12D) protein release from cancer cells succumbing to autophagy-dependent ferroptosis. Extracellular KRAS(G12D) packaged into exosomes then is taken up by macrophages through an AGER-dependent mechanism. KRAS(G12D) causes macrophages to switch to an M2-like pro-tumor phenotype via STAT3-dependent fatty acid oxidation. Consequently, the disruption of KRAS(G12D) release and uptake can abolish the macrophage-mediated stimulation of pancreatic adenocarcinomas in mouse models. Importantly, the level of KRAS(G12D) expression in macrophages correlates with poor survival in pancreatic cancer patients. These findings not only identify extracellular KRAS(G12D) as a key mediator of cancer cell-macrophage communication, but also provide a novel KRAS-targeted anticancer strategy.
推荐引用方式
GB/T 7714：

Dai Enyong,Han Leng,Liu Jiao, et al. Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein [J].AUTOPHAGY,2020,16(11):2069-2083.
APA：

Dai Enyong,Han Leng,Liu Jiao,Xie Yangchun,&Tang Daolin.(2020).Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein .AUTOPHAGY,16(11):2069-2083.
MLA：

Dai Enyong, et al. "Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein" .AUTOPHAGY 16,11(2020):2069-2083.
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