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Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment | |
Tang, Shijie1,13; Xue, Yun1,2,13; Qin, Zhen1,13; Fang, Zhaoyuan1,3,13,14; Sun, Yihua3,4,13; Yuan, Chongzhe3,4,13; Pan, Yunjian3,4,13; Zhao, Yue3,4,13; Tong, Xinyuan1,13; Zhang, Jian1,13; Huang, Hsinyi1,13; Chen, Yuting1,6,13 ![]() ![]() ![]() | |
2023-04-01 | |
发表期刊 | NATIONAL SCIENCE REVIEW (IF:16.3[JCR-2023],18.6[5-Year]) |
ISSN | 2095-5138 |
EISSN | 2053-714X |
卷号 | 10期号:4 |
DOI | 10.1093/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 |
URL | 查看原文 |
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) |
引用统计 | 正在获取...
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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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