Elevated Nuclear PHGDH Synergistically Functions with cMyc to Reshape the Immune Microenvironment of Liver Cancer
文献类型：期刊论文
| 作者 | Zhu, Hongwen3; Yu, Hua2; Zhou, Hu3 ; Zhu, Wencheng1; Wang, Xiongjun2
|
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2023-06-01 |
| 卷号 | 10期号:17 |
| 关键词 | cMyc CXCL1 IL8 liver cancer neutrophil nuclear PHGDH |
| DOI | 10.1002/advs.202205818 |
| 文献子类 | Article |
| 英文摘要 | Herein, we observed that nuclear localization of phosphoglycerate dehydrogenase (PHGDH) is associated with poor prognosis in liver cancer, and Phgdh is required for liver cancer progression in a mouse model. Unexpectedly, impairment of Phgdh enzyme activity exerts a slight effect in a liver cancer model. In liver cancer cells, the aspartate kinase-chorismate mutase-tyrA prephenate dehydrogenase (ACT) domain of PHGDH binds nuclear cMyc to form a transactivation axis, PHGDH/p300/cMyc/AF9, which drives chemokine CXCL1 and IL8 gene expression. Then, CXCL1 and IL8 promote neutrophil recruitment and enhance tumor-associated macrophage (TAM) filtration in the liver, thereby advancing liver cancer. Forced cytosolic localization of PHGDH or destruction of the PHGDH/cMyc interaction abolishes the oncogenic function of nuclear PHGDH. Depletion of neutrophils by neutralizing antibodies greatly hampers TAM filtration. These findings reveal a nonmetabolic role of PHGDH with altered cellular localization and suggest a promising drug target for liver cancer therapy by targeting the nonmetabolic region of PHGDH. |
| WOS关键词 | TUMOR-ASSOCIATED MACROPHAGES ; TARGETING C-MYC ; EXPRESSION ; GENE ; GROWTH ; TRANSCRIPTION ; TRANSFECTION ; INTEGRATION ; CHEMOKINES ; TRANSPOSON |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000972543200001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309640]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhou, Hu; Zhu, Wencheng; Wang, Xiongjun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techno, Shanghai 200031, Peoples R China 2.Guangzhou Univ, Precise Genome Engn Ctr, Sch Life Sci, Guangzhou 510006, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhu, Hongwen,Yu, Hua,Zhou, Hu,et al. Elevated Nuclear PHGDH Synergistically Functions with cMyc to Reshape the Immune Microenvironment of Liver Cancer[J]. ADVANCED SCIENCE,2023,10(17). |
| APA | Zhu, Hongwen,Yu, Hua,Zhou, Hu,Zhu, Wencheng,&Wang, Xiongjun.(2023).Elevated Nuclear PHGDH Synergistically Functions with cMyc to Reshape the Immune Microenvironment of Liver Cancer.ADVANCED SCIENCE,10(17). |
| MLA | Zhu, Hongwen,et al."Elevated Nuclear PHGDH Synergistically Functions with cMyc to Reshape the Immune Microenvironment of Liver Cancer".ADVANCED SCIENCE 10.17(2023). |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。