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DOI | 10.1038/ncomms15469 |
The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression | |
Ma, Biao1; Cheng, Hongcheng1; Mu, Chenglong1; Geng, Guangfeng1; Zhao, Tian1; Luo, Qian1; Ma, Kaili1; Chang, Rui1; Liu, Qiangqiang1; Gao, Ruize1; Nie, Junli1; Xie, Jiaying1; Han, Jinxue1; Chen, Linbo1; Ma, Gui1; Zhu, Yushan1; Chen, Quan1,2 | |
2019-03-04 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China |
英文摘要 | The interactions between tumor cells with their microenvironments, including hypoxia, acidosis and immune cells, lead to the tumor heterogeneity which promotes tumor progression. Here, we show that SIAH2-NRF1 axis remodels tumor microenvironment through regulating tumor mitochondrial function, tumor-associated macrophages (TAMs) polarization and cell death for tumor maintenance and progression. Mechanistically, low mitochondrial gene expression in breast cancers is associated with a poor clinical outcome. The hypoxia-activated E3 ligase SIAH2 spatially downregulates nuclear-encoded mitochondrial gene expression including pyruvate dehydrogenase beta via degrading NRF1 (Nuclear Respiratory Factor 1) through ubiquitination on lysine 230, resulting in enhanced Warburg effect, metabolic reprogramming and pro-tumor immune response. Dampening NRF1 degradation under hypoxia not only impairs the polarization of TAMs, but also promotes tumor cells to become more susceptible to apoptosis in a FADD-dependent fashion, resulting in secondary necrosis due to the impairment of efferocytosis. These data represent that inhibition of NRF1 degradation is a potential therapeutic strategy against cancer. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000460125400016 |
WOS关键词 | MITOCHONDRIAL BIOGENESIS ; HYPOXIC REGULATION ; MACROPHAGES ; EXPRESSION ; CELLS ; RESPIRATION ; METASTASIS ; METABOLISM ; MUTATIONS ; PHENOTYPE |
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/203308 |
专题 | 资源环境科学 |
作者单位 | 1.Nankai Univ, State Key Lab Med Chem Biol, Tianjin Key Lab Prot Sci, Coll Life Sci, Tianjin 300071, Peoples R China; 2.Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing 100101, Peoples R China |
推荐引用方式 GB/T 7714 | Ma, Biao,Cheng, Hongcheng,Mu, Chenglong,et al. The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Ma, Biao.,Cheng, Hongcheng.,Mu, Chenglong.,Geng, Guangfeng.,Zhao, Tian.,...&Chen, Quan.(2019).The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression.NATURE COMMUNICATIONS,10. |
MLA | Ma, Biao,et al."The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
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