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Targeting TFAP2Dcondensation suppresses the development of esophageal squamous cell carcinoma

文献类型：期刊论文

作者Deng, Zhaomin4,5; Pu, Lu4,6; Deng, Kai3,7; Liu, Wencheng2; Zhang, Jifa1; Zhang, Liang9,10; Meng, Qian8; Zhou, Wanwan10; Jin, Haoran3,7; Xu, Dongqin4,6
刊名CELL
出版日期2026-02-05
卷号189期号:3页码:45
ISSN号0092-8674
DOI10.1016/j.cell.2025.11.019
英文摘要Exploring targeted therapies for esophageal squamous cell carcinoma (ESCC) remains challenging. Although investigating the roles and therapeutic applications of liquid-liquid phase separation (LLPS) is increasingly of interest, its relationship with ESCC remains unclear. After improving the assay for transposase-accessible chromatin using sequencing (ATAC-seq) protocol for limited-amount clinical samples, we unravel transcription factor AP-2 beta (TFAP2D) as a key downregulated transcription factor (TF) through combined chromatin accessibility and gene expression analyses with cancerous and paracancerous tissues from early-stage ESCC patients. TFAP2D undergoes condensation in the nucleus to bind the zinc finger protein 131 (ZNF131) promoter, thereby inhibiting ZNF131 expression and ESCC progression. The other two crucial downregulated TFs uncovered are incorporated into TFAP2D condensates to bind their corresponding target, suggesting that LLPS may be a hallmark of ESCC transcription. In addition, we obtained compound A6 that mediates intrinsically disordered region conformational changes to enhance TFAP2D condensation and specific ESCC suppression in cells, mice, and patient-derived organoids. Thus, we indicate an LLPSmediated transcriptional mechanism and a potential therapeutic approach for ESCC.
WOS关键词LIQUID PHASE-SEPARATION ; CANCER ; PROTEIN ; EXPRESSION ; ORGANOIDS ; VISUALIZATION ; VALIDATION ; ACTIVATION ; MECHANISMS ; RESISTANCE
资助项目National Key Research and Development Program of China[2024YFE0104700] ; National Natural Science Foundation of China[82470536] ; National Natural Science Foundation of China[82425054] ; National Natural Science Foundation of China[32090043] ; Sichuan University-University of Oxford Huaxi Joint Center for Gastrointestinal Cancer Agreement Project[161200021] ; National Clinical Research Center for Geriatrics[Z2024JC003]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:001686961100001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/322978]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Ke, Bowen; Kerr, David J.; Yang, Li; Yang, Jinlin; Jiang, Hao
作者单位1.Sichuan Univ, West China Hosp, Dept Neurol, Lab Neurosyst & Multimorbid, Chengdu 610041, Peoples R China
2.Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Dept Anesthesiol,Lab Anesthesia & Crit Care Med, Chengdu 610041, Peoples R China
3.Sichuan Univ, West China Hosp, Dept Gastroenterol & Hepatol, Chengdu 610041, Peoples R China
4.Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Lab Aging & Canc, Chengdu 610041, Peoples R China
5.Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Dept Med Genet, Chengdu 610041, Peoples R China
6.Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Lab Aging & Canc, Chengdu 610041, Peoples R China
7.Sichuan Univ, Sichuan Univ Univ Oxford Huaxi Joint Ctr Gastroint, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Chengdu 610041, Peoples R China
8.Shanghai Inst Mat Med, Chinese Acad Sci, Dept Analyt Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China
9.Tianjin Univ, Sch Synthet Biol & Biomfg, Tianjin 300072, Peoples R China
10.Univ Sci & Technol China, Ctr Adv Interdisciplinary Sci & Biomed IHM, Hefei Natl Res Ctr Cross Disciplinary Sci,Div Life, Minist Educ,Key Lab Membraneless Organelles & Cell, Hefei 230027, Peoples R China
推荐引用方式
GB/T 7714		 Deng, Zhaomin,Pu, Lu,Deng, Kai,et al. Targeting TFAP2Dcondensation suppresses the development of esophageal squamous cell carcinoma[J]. CELL,2026,189(3):45.
APA Deng, Zhaomin.,Pu, Lu.,Deng, Kai.,Liu, Wencheng.,Zhang, Jifa.,...&Jiang, Hao.(2026).Targeting TFAP2Dcondensation suppresses the development of esophageal squamous cell carcinoma.CELL,189(3),45.
MLA Deng, Zhaomin,et al."Targeting TFAP2Dcondensation suppresses the development of esophageal squamous cell carcinoma".CELL 189.3(2026):45.

入库方式： OAI收割

来源：上海药物研究所

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