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Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment
2023-04-01
发表期刊NATIONAL SCIENCE REVIEW (IF:16.3[JCR-2023],18.6[5-Year])
ISSN2095-5138
EISSN2053-714X
卷号10期号:4
DOI10.1093/nsr/nwad028
摘要Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, harbors strong plasticity and is significantly associated with poor prognosis. We established an up-to-date comprehensive genomic and transcriptomic landscape of LUAS in 109 Chinese specimens and demonstrated LUAS development via adeno-to-squamous transdifferentiation. Unsupervised transcriptomic clustering and dynamic network biomarker analysis identified an inflammatory subtype as the critical transition stage during LUAS development. Dynamic dysregulation of the counteracting lineage-specific transcription factors (TFs), containing adenomatous TFs NKX2-1 and FOXA2, and squamous TFs TP63 and SOX2, finely tuned the lineage transition via promoting CXCL3/5-mediated neutrophil infiltration. Genomic clustering identified the most malignant subtype featured with STK11-inactivation, and targeting LSD1 through genetic deletion or pharmacological inhibition almost eradicated STK11-deficient lung tumors. These data collectively uncover the comprehensive molecular landscape, oncogenic driver spectrum and therapeutic vulnerability of Chinese LUAS. © 2023 The Author(s). Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.
关键词Biological organs Diagnosis Genome Transcription Tumors ALK fusion Counteracting transcription factor regulatory network CXCL3/CXCL5 Genomics LSD1 LUAS Microenvironments Regulatory network Transcriptomics Transdifferentiation
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收录类别EI
语种英语
出版者Oxford University Press
EI入藏号20232114116431
EI主题词Transcription factors
EI分类号461.2 Biological Materials and Tissue Engineering ; 461.6 Medicine and Pharmacology ; 461.9 Biology
原始文献类型Journal article (JA)
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/306475
专题生命科学与技术学院
生命科学与技术学院_特聘教授组_季红斌组
生命科学与技术学院_特聘教授组_陈洛南组
生命科学与技术学院_博士生
通讯作者Chen, Luonan; Ji, Hongbin
作者单位
1.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai; 200031, China;
2.College of Life Sciences, University of Chinese Academy of Sciences, Beijing; 100049, China;
3.Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai; 200032, China;
4.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai; 200032, China;
5.Department of Mathematics, Shanghai University, Shanghai; 200444, China;
6.School of Life Science and Technology, Shanghai Tech University, Shanghai; 200120, China;
7.Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Cologne; 50931, Germany;
8.Department of Pathology, University Hospital Cologne, Cologne; 50937, Germany;
9.Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York; NY; 10065, United States;
10.Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York; NY; 10016, United States;
11.Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai; 200031, China;
12.School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou; 310024, China;
13.Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining; 314400, China;
14.Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou; 310000, China
通讯作者单位生命科学与技术学院
推荐引用方式
GB/T 7714
Tang, Shijie,Xue, Yun,Qin, Zhen,et al. Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment[J]. NATIONAL SCIENCE REVIEW,2023,10(4).
APA Tang, Shijie.,Xue, Yun.,Qin, Zhen.,Fang, Zhaoyuan.,Sun, Yihua.,...&Ji, Hongbin.(2023).Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment.NATIONAL SCIENCE REVIEW,10(4).
MLA Tang, Shijie,et al."Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment".NATIONAL SCIENCE REVIEW 10.4(2023).
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