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Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis

文献类型：期刊论文

作者Jin, Yujuan2,3,4; Zhao, Qiqi2,3,4; Zhu, Weikang1; Feng, Yan2,3,4; Xiao, Tian5; Zhang, Peng6; Jiang, Liyan7; Hou, Yingyong8; Guo, Chenchen2,3,4; Huang, Hsinyi2,3,4
刊名NATIONAL SCIENCE REVIEW
出版日期2022-07-01
卷号9期号:7页码:15
ISSN号2095-5138
关键词small cell lung cancer SWI SNF complex TAZ phenotypic transition metastasis
DOI10.1093/nsr/nwab232
英文摘要Small-cell lung cancer (SCLC) is a recalcitrant cancer characterized by high metastasis. However, the exact cell type contributing to metastasis remains elusive. Using a Rb1(L/L)/Trp53(L/L) mouse model, we identify the NCAM(hi)CD44(lo/-) subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAM(lo)CD44(hi) cell (non-SMC). Integrative chromatin accessibility and gene expression profiling studies reveal the important role of the SWI/SNF complex, and knockout of its central component, Brg1, significantly inhibits such phenotypic transition and metastasis. Mechanistically, TAZ is silenced by the SWI/SNF complex during SCLC malignant progression, and its knockdown promotes SMC transition and metastasis. Importantly, ectopic TAZ expression reversely drives SMC-to-non-SMC transition and alleviates metastasis. Single-cell RNA-sequencing analyses identify SMC as the dominant subpopulation in human SCLC metastasis, and immunostaining data show a positive correlation between TAZ and patient prognosis. These data uncover high SCLC plasticity and identify TAZ as the key molecular switch in orchestrating SCLC phenotypic transition and metastasis.
资助项目National Natural Science Foundation of China[81871875] ; National Natural Science Foundation of China[82173340] ; National Natural Science Foundation of China[82030083] ; National Natural Science Foundation of China[81872312] ; National Natural Science Foundation of China[82011540007] ; National Natural Science Foundation of China[31621003] ; National Natural Science Foundation of China[81402371] ; National Natural Science Foundation of China[12025107] ; National Basic Research Program of China[2017YFA0505501] ; National Basic Research Program of China[2020YFA0803300] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19020201] ; Basic Frontier Scientific Research Program of the Chinese Academy of Sciences[ZDBSLY-SM006] ; International Cooperation Project of the Chinese Academy of Sciences[153D31KYSB20190035] ; Innovative Research Team of High-Level Local Universities in Shanghai[SSMU-ZLCX20180500] ; Science and Technology Commission of Shanghai Municipality[21ZR1470300]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者OXFORD UNIV PRESS
WOS记录号WOS:000883232400001
源URL[http://ir.amss.ac.cn/handle/2S8OKBNM/60698]  
专题应用数学研究所
通讯作者Wang, Yong; Hu, Liang; Ji, Hongbin
作者单位1.Chinese Acad Sci, Key Lab Management Decis & Informat Syst, Natl Ctr Math & Interdisciplinary Sci,Acad Math &, Ctr Excellence Math Sci,Hua Loo Keng Ctr Math Sci, Beijing 100190, Peoples R China
2.Chinese Acad Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China
4.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China
5.Shenzhen Univ, Shenzhen Key Lab Translat Med Tumor, Dept Cell Biol & Genet, Hlth Sci Ctr, Shenzhen 518060, Peoples R China
6.Tongji Univ, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China
7.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai 200030, Peoples R China
8.Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China
9.Fudan Univ, Dept Pathol, Sch Basic Med Sci, Shanghai 200032, Peoples R China
10.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China
推荐引用方式
GB/T 7714		 Jin, Yujuan,Zhao, Qiqi,Zhu, Weikang,et al. Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis[J]. NATIONAL SCIENCE REVIEW,2022,9(7):15.
APA Jin, Yujuan.,Zhao, Qiqi.,Zhu, Weikang.,Feng, Yan.,Xiao, Tian.,...&Ji, Hongbin.(2022).Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis.NATIONAL SCIENCE REVIEW,9(7),15.
MLA Jin, Yujuan,et al."Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis".NATIONAL SCIENCE REVIEW 9.7(2022):15.

入库方式： OAI收割

来源：数学与系统科学研究院

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