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

doi:10.1093/nsr/nwab232

	Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis
	Jin, Yujuan 1,2,3; Zhao, Qiqi1,2,3,4 ; Zhu, Weikang 5; Feng, Yan 1,2,3; Xiao, Tian 6; Zhang, Peng 7; Jiang, Liyan 8; Hou, Yingyong 9; Guo, Chenchen 1,2,3; Huang, Hsinyi 1,2,3; Chen, Yabin 1,2,3; Tong, Xinyuan 1,2,3; Cao, Jiayu 1,2,3; Li, Fei 10; Zhu, Xueliang1,2,3,4 ; Qin, Jun 11; Gao, Dong 1,2,3; Liu, Xin-Yuan 1,2,3; Zhang, Hua 12; Chen, Luonan 1,2,3,14; Thomas, Roman K.13,15; Wong, Kwok-Kin 12; Zhang, Lei 1,2,3,14; Wang, Yong 5,14; Hu, Liang 1,2,3; Ji, Hongbin1,2,3,4,14
	2022-01-04
发表期刊	NATIONAL SCIENCE REVIEW (IF:16.3[JCR-2023],18.6[5-Year])
ISSN	2053-714X
EISSN	2053-714X
卷号	9 期号:7
发表状态	已发表
DOI	10.1093/nsr/nwab232
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 Rb1L/L/Trp53L/L mouse model, we identify the NCAMhiCD44lo/– subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAMloCD44hi 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.
关键词	small cell lung cancer SWI/SNF complex TAZ phenotypic transition metastasis
URL	查看原文
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000883232400001
出版者	OXFORD UNIV PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/243573
专题	生命科学与技术学院_博士生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_朱学良组
共同第一作者	Zhao, Qiqi; Zhu, Weikang; Feng, Yan; Xiao, Tian
通讯作者	Wang, Yong; Hu, Liang; Ji, Hongbin
作者单位	1.Chinese Acad Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 3.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China 5.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 6.Shenzhen Univ, Shenzhen Key Lab Translat Med Tumor, Dept Cell Biol & Genet, Hlth Sci Ctr, Shenzhen 518060, Peoples R China 7.Tongji Univ, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China 8.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai 200030, Peoples R China 9.Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China 10.Fudan Univ, Dept Pathol, Sch Basic Med Sci, Shanghai 200032, Peoples R China 11.Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Nutr & Hlth Sci, Shanghai 200031, Peoples R China 12.New York Univ, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA 13.Univ Cologne, Dept Translat Gen, Ctr Integrated Oncol, D-50931 Cologne, Germany 14.Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China 15.Univ Hosp Cologne, Dept Pathol, D-50937 Cologne, Germany
通讯作者单位	生命科学与技术学院
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).
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).
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).