EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation

doi:10.1084/jem.20232028

	EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation
	Qin, Zhen 1; Yue, Meiting 1,2; Tang, Shijie 1; Wu, Fengying 3; Sun, Honghua 1,2; Li, Yuan 6,10; Zhang, Yongchang 7; Izumi, Hiroki 8; Huang, Hsinyi 9; Wang, Wanying 3; Xue, Yun 1,20; Tong, Xinyuan 1; Mori, Shunta 8; Taki, Tetsuro 8; Goto, Koichi 8; Jin, Yujuan 1; Li, Fei 10; Li, Fu-Ming 11; Gao, Yijun 12; Fang, Zhaoyuan 13; Fang, Yisheng 14; Hu, Liang 1; Yan, Xiumin 15; Xu, Guoliang16,19 ; Chen, Haiquan 6,10; Kobayashi, Susumu S.17; Ventura, Andrea 18; Wong, Kwok-Kin 9; Zhu, Xueliang1,2,19 ; Chen, Liang 4,5; Ren, Shengxiang 3; Chen, Luo-Nan1,2,19,20 ; Ji, Hongbin1,2,19,20
	2024-01-29
发表期刊	JOURNAL OF EXPERIMENTAL MEDICINE (IF:12.6[JCR-2023],14.1[5-Year])
ISSN	0022-1007
EISSN	1540-9538
卷号	221 期号:3
发表状态	已发表
DOI	10.1084/jem.20232028
摘要	["Through integrative analyses of mouse models and clinical data, Qin et al. find that certain ALK-rearranged LUAD hold the potential toward squamous transition. Such phenotypic transition associates with TKI resistance and relies on the JAK-STAT signaling.","Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, exhibits strong cancer plasticity. We find that ALK rearrangement is detectable in 5.1-7.5% of human LUAS, and transgenic expression of EML4-ALK drives lung adenocarcinoma (LUAD) formation initially and squamous transition at late stage. We identify club cells as the main cell-of-origin for squamous transition. Through recapitulating lineage transition in organoid system, we identify JAK-STAT signaling, activated by EML4-ALK phase separation, significantly promotes squamous transition. Integrative study with scRNA-seq and immunostaining identify a plastic cell subpopulation in ALK-rearranged human LUAD showing squamous biomarker expression. Moreover, those relapsed ALK-rearranged LUAD show notable upregulation of squamous biomarkers. Consistently, mouse squamous tumors or LUAD with squamous signature display certain resistance to ALK inhibitor, which can be overcome by combined JAK1/2 inhibitor treatment. This study uncovers strong plasticity of ALK-rearranged tumors in orchestrating phenotypic transition and drug resistance and proposes a potentially effective therapeutic strategy."]
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收录类别	SCI
语种	英语
WOS研究方向	Immunology ; Research & Experimental Medicine
WOS类目	Immunology ; Medicine, Research & Experimental
WOS记录号	WOS:001209121900001
出版者	ROCKEFELLER 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/372859
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_徐国良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_特聘教授组_朱学良组
通讯作者	Zhu, Xueliang; Chen, Liang; Ren, Shengxiang; Chen, Luo-Nan; Ji, Hongbin
作者单位	1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Med Oncol, Shanghai, Peoples R China 4.Jinan Univ, Key Lab Tumor Mol Biol, Minist Educ, Guangzhou, Peoples R China 5.Jinan Univ, Guangdong Higher Educ Inst, Inst Life & Hlth Engn, Key Lab Funct Prot Res, Guangzhou, Peoples R China 6.Fudan Univ, Shanghai Canc Ctr, Dept Thorac Surg, Shanghai, Peoples R China 7.Cent South Univ, Hunan Canc Hosp, Dept Med Oncol, Changsha, Peoples R China 8.Natl Canc Ctr Hosp East, Dept Thorac Oncol, Kashiwa, Japan 9.NYU, NYU Grossman Sch Med, Langone Hlth, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA 10.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China 11.Fudan Univ, Inst Metab & Integrat Biol, Shanghai Key Lab Metab Remodeling & Hlth, Shanghai, Peoples R China 12.Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Guangzhou, Peoples R China 13.Zhejiang Univ, Univ Edinburgh Inst, Haining, Peoples R China 14.Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Peoples R China 15.Shanghai Jiao Tong Univ, Xinhua Hosp, Inst Early Life Hlth,Sch Med, Minist Educ,Shanghai Key Lab Childrens Environm Hl, Shanghai, Peoples R China 16.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol, Shanghai, Peoples R China 17.Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Div Translat Genom, Kashiwa, Japan 18.Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY USA 19.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 20.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Hangzhou, Peoples R 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	Qin, Zhen,Yue, Meiting,Tang, Shijie,et al. EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2024,221(3).
APA	Qin, Zhen.,Yue, Meiting.,Tang, Shijie.,Wu, Fengying.,Sun, Honghua.,...&Ji, Hongbin.(2024).EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation.JOURNAL OF EXPERIMENTAL MEDICINE,221(3).
MLA	Qin, Zhen,et al."EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation".JOURNAL OF EXPERIMENTAL MEDICINE 221.3(2024).