Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition

doi:10.1038/s41467-019-09295-7

	Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition
	Gao, Lei 1,2; Hu, Yong 1; Tian, Yahui 1; Fan, Zhenzhen 1,3; Wang, Kun 4; Li, Hongdan 1; Zhou, Qian 1; Zeng, Guandi 1; Hu, Xin 5; Yu, Lei 6; Zhou, Shiyu 7,8,9; Tong, Xinyuan 7,8,9,10; Huang, Hsinyi 7,8,9; Chen, Haiquan 11; Liu, Qingsong 12; Liu, Wanting 1; Zhang, Gong 1; Zeng, Musheng 13; Zhou, Guangbiao 14,15; He, Qingyu 1; Ji, Hongbin7,8,9,16 ; Chen, Liang 1
	2019-04-10
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	10
发表状态	已发表
DOI	10.1038/s41467-019-09295-7
摘要	Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes remain to be systemically identified for lung cancer. Through the genome-wide screening of tumor-suppressive transcription factors, we demonstrate here that GATA4 functions as an essential tumor suppressor in lung cancer in vitro and in vivo. Ectopic GATA4 expression results in lung cancer cell senescence. Mechanistically, GATA4 upregulates multiple miRNAs targeting TGFB2 mRNA and causes ensuing WNT7B downregulation and eventually triggers cell senescence. Decreased GATA4 level in clinical specimens negatively correlates with WNT7B or TGF-beta 2 level and is significantly associated with poor prognosis. TGFBR1 inhibitors show synergy with existing therapeutics in treating GATA4-deficient lung cancers in genetically engineered mouse model as well as patient-derived xenograft (PDX) mouse models. Collectively, our work demonstrates that GATA4 functions as a tumor suppressor in lung cancer and targeting the TGF-beta signaling provides a potential way for the treatment of GATA4-deficient lung cancer.
收录类别	SCI ; SCIE
语种	英语
资助项目	Chinese Academy of Science Taiwan Young Scholar Visiting Program[2015TW1SB0001]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000463984400014
出版者	NATURE PUBLISHING GROUP
WOS关键词	REGULATORY T-CELLS ; TRANSCRIPTION FACTORS ; PROMOTER METHYLATION ; BETA-CATENIN ; KINASE ; GENE ; PROGRESSION ; ACTIVATION ; SENESCENCE ; PATHWAY
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/34328
专题	生命科学与技术学院_特聘教授组_季红斌组
通讯作者	He, Qingyu; Ji, Hongbin; Chen, Liang
作者单位	1.Jinan Univ, Coll Life Sci & Technol, Inst Life & Hlth Engn, Key Lab Funct Prot Res Guangdong Higher Educ, Guangzhou 510632, Guangdong, Peoples R China 2.Beijing Normal Univ, Coll Life Sci, Beijing 100875, Peoples R China 3.China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China 4.Chinese Acad Sci, Inst Automat, Key Lab Mol Imaging, Beijing 100190, Peoples R China 5.Univ Texas Hlth Sci Ctr Houston UTHlth, 2450 Holcombe Blvd,Suite 1, Houston, TX 77021 USA 6.Capital Med Univ, Beijing Tongren Hosp, Beijing 100730, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 8.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China 9.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Innovat Ctr Cell Signaling Network, Shanghai 200031, Peoples R China 10.Univ Chinese Acad Sci, Beijing, Peoples R China 11.Fudan Univ, Dept Thorac Surg, Shanghai Canc Ctr, Shanghai 200032, Peoples R China 12.Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Anhui, Peoples R China 13.Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, Guangzhou, Guangdong, Peoples R China 14.Chinese Acad Med Sci, Natl Canc Ctr, Canc Hosp, State Key Lab Mol Oncol, Beijing 100021, Peoples R China 15.Peking Union Med Coll, Beijing 100021, Peoples R China 16.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, 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	Gao, Lei,Hu, Yong,Tian, Yahui,et al. Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition[J]. NATURE COMMUNICATIONS,2019,10.
APA	Gao, Lei.,Hu, Yong.,Tian, Yahui.,Fan, Zhenzhen.,Wang, Kun.,...&Chen, Liang.(2019).Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition.NATURE COMMUNICATIONS,10.
MLA	Gao, Lei,et al."Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition".NATURE COMMUNICATIONS 10(2019).