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DOI | 10.1038/s41467-019-11072-5 |
A novel Fer/FerT targeting compound selectively evokes metabolic stress and necrotic death in malignant cells | |
Elkis, Yoav1; Cohen, Moshe1; Yaffe, Etai1; Satmary-Tusk, Shirly1; Feldman, Tal1; Hikri, Elad1; Nyska, Abraham2,3; Feiglin, Ariel1; Ofran, Yanay1; Shpungin, Sally1; Nir, Uri1 | |
2019-07-19 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Israel |
英文摘要 | Disruption of the reprogrammed energy management system of malignant cells is a prioritized goal of targeted cancer therapy. Two regulators of this system are the Fer kinase, and its cancer cell specific variant, FerT, both residing in subcellular compartments including the mitochondrial electron transport chain. Here, we show that a newly developed inhibitor of Fer and FerT, E260, selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation, and onset of energy-consuming autophagy which decreases the cellular ATP level. Notably, Fer was also found to associate with PARP-1 and E260 disrupted this association thereby leading to PARP-1 activation. The cooperative intervention with these metabolic pathways leads to energy crisis and necrotic death in malignant, but not in normal human cells, and to the suppression of tumors growth in vivo. Thus, E260 is a new anti-cancer agent which imposes metabolic stress and cellular death in cancer cells. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000412999700008 |
WOS关键词 | TYROSINE KINASE ; CANCER-CELLS ; POLY(ADP-RIBOSE) POLYMERASE ; POOR-PROGNOSIS ; APOPTOSIS ; AUTOPHAGY ; PHOSPHORYLATION ; EXPRESSION ; NECROSIS ; INHIBITION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204460 |
专题 | 资源环境科学 |
作者单位 | 1.Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel; 2.Timrat, Toxicol Pathol, IL-36576 Tel Aviv, Israel; 3.Tel Aviv Univ, Sackler Sch Med, IL-36576 Tel Aviv, Israel |
推荐引用方式 GB/T 7714 | Elkis, Yoav,Cohen, Moshe,Yaffe, Etai,et al. A novel Fer/FerT targeting compound selectively evokes metabolic stress and necrotic death in malignant cells[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Elkis, Yoav.,Cohen, Moshe.,Yaffe, Etai.,Satmary-Tusk, Shirly.,Feldman, Tal.,...&Nir, Uri.(2019).A novel Fer/FerT targeting compound selectively evokes metabolic stress and necrotic death in malignant cells.NATURE COMMUNICATIONS,8. |
MLA | Elkis, Yoav,et al."A novel Fer/FerT targeting compound selectively evokes metabolic stress and necrotic death in malignant cells".NATURE COMMUNICATIONS 8(2019). |
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