南方科技大学知识苑(SUSTech KC): BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma

题名	BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma
作者	Feng，Yuliang1 ; Cai，Liuyang2 ; Pook，Martin 1; Liu，Feng 1; Chang，Chao Hui 1; Mouti，Mai Abdel 1; Nibhani，Reshma 1; Militi，Stefania 1; Dunford，James 1; Philpott，Martin 1; Fan，Yanbo 3,4; Fan，Guo Chang 5; Liu，Qi 6; Qi，Jun 6; Wang，Cheng 7; Hong，Wanzi 8; Morgan，Hannah 9; Wang，Mingyang 10; Sadayappan，Sakthivel 9; Jegga，Anil G.11,12,13; Oppermann，Udo 1,14; Wang，Yigang 15; Huang，Wei 9; Jiang，Lei 8; Pauklin，Siim 1
通讯作者	Wang，Yigang; Huang，Wei; Jiang，Lei; Pauklin，Siim
共同第一作者	Feng，Yuliang; Cai，Liuyang; Pook，Martin; Liu，Feng
发表日期	2023
DOI	10.1053/j.gastro.2023.09.021
发表期刊	Gastroenterology 影响因子和分区
ISSN	0016-5085
EISSN	1528-0012
卷号	166 期号:1页码:139-154
摘要	Background & Aims: The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence of pancreatic cancer stem-like cells (CSCs) that respond poorly to current chemotherapy regimens. The epigenetic mechanisms regulating CSCs are currently insufficiently understood, which hampers the development of novel strategies for eliminating CSCs. Methods: By small molecule compound screening targeting 142 epigenetic enzymes, we identified that bromodomain-containing protein BRD9, a component of the BAF histone remodeling complex, is a key chromatin regulator to orchestrate the stemness of pancreatic CSCs via cooperating with the TGFβ/Activin-SMAD2/3 signaling pathway. Results: Inhibition and genetic ablation of BRD9 block the self-renewal, cell cycle entry into G0 phase and invasiveness of CSCs, and improve the sensitivity of CSCs to gemcitabine treatment. In addition, pharmacological inhibition of BRD9 significantly reduced the tumorigenesis in patient-derived xenografts mouse models and eliminated CSCs in tumors from pancreatic cancer patients. Mechanistically, inhibition of BRD9 disrupts enhancer-promoter looping and transcription of stemness genes in CSCs. Conclusions: Collectively, the data suggest BRD9 as a novel therapeutic target for PDAC treatment via modulation of CSC stemness.
关键词	Cancer Stem Cells Cancer Therapy Epigenetics Pancreatic Cancer TGFβ/Activin-SMAD2/3
相关链接	[Scopus记录]
收录类别	SCI
语种	英语
重要成果	NI论文
学校署名	共同第一 ; 其他
资助项目	Natural Science Foundation of Guangdong Province[2018A030313029] ; Pancreatic Cancer UK[2018RIF_03] ; National Natural Science Foundation of China[81800262] ; National Institutes of Health[R01 AR078001] ; National Institutes of Health[R01 HL105826] ; National Institutes of Health[R01 HL130356] ; National Institutes of Health[R01 HL143490] ; National Institutes of Health[R01 HL143490] ; National Institutes of Health[R01 HL157456] ; National Institutes of Health[R01 HL163148] ; National Institutes of Health[R38 HL155775]
ESI学科分类	CLINICAL MEDICINE
Scopus记录号	2-s2.0-85177217970
来源库	Scopus
引用统计	被引频次[WOS]：4
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/619698
专题	南方科技大学医学院_药理学系工学院南方科技大学医学院工学院_计算机科学与工程系
作者单位	1.Botnar Research Centre,Nuffield Department of Orthopaedics,Rheumatology and Musculoskeletal Sciences,University of Oxford,Oxford,United Kingdom 2.Department of Pharmacology,School of Medicine,Southern University of Science and Technology,Guangdong,China 3.Department of Cancer Biology,University of Cincinnati College of Medicine,Cincinnati,United States 4.Department of Internal Medicine,Division of Cardiovascular Health and Disease,University of Cincinnati College of Medicine,Cincinnati,United States 5.Departments of Pharmacology and Systems Physiology,University of Cincinnati College of Medicine,Cincinnati,United States 6.Department of Cancer Biology,Dana-Farber Cancer Institute,Boston,United States 7.Smurfit Institute of Genetics,Trinity College Dublin,Dublin,Ireland 8.Department of Cardiology,Guangdong Cardiovascular Institute,Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences),Southern Medical University,China 9.Heart,Lung and Vascular Institute,Department of Internal Medicine,Division of Cardiovascular Health and Disease,University of Cincinnati,Cincinnati,United States 10.College of Engineering and Applied Science,University of Cincinnati,Cincinnati,United States 11.Division of Biomedical Informatics,Cincinnati Children's Hospital Medical Center,Cincinnati,United States 12.Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,United States 13.Department of Computer Science,University of Cincinnati College of Engineering,Cincinnati,United States 14.Oxford Translational Myeloma Centre,Botnar Research Centre,Oxford,United Kingdom 15.Department of Pathology and Laboratory Medicine,University of Cincinnati College of Medicine,Cincinnati,United States
推荐引用方式 GB/T 7714	Feng，Yuliang,Cai，Liuyang,Pook，Martin,et al. BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma[J]. Gastroenterology,2023,166(1):139-154.
APA	Feng，Yuliang.,Cai，Liuyang.,Pook，Martin.,Liu，Feng.,Chang，Chao Hui.,...&Pauklin，Siim.(2023).BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma.Gastroenterology,166(1),139-154.
MLA	Feng，Yuliang,et al."BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma".Gastroenterology 166.1(2023):139-154.

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