Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma
文献类型：期刊论文
| 作者 | Peng, Li4,5; Jiang, Yanyi3; Chen, Hengxing4; Wang, Yongqiang4,5; Lan, Qiusheng2; Chen, Shuiqin4,5; Huang, Zhanwang4,5; Zhang, Jingyuan4,5; Tian, Duanqing4,5; Qiu, Yuntan4 |
| 刊名 | ACTA PHARMACEUTICA SINICA B
 |
| 出版日期 | 2024-05-01 |
| 卷号 | 14 |
| 关键词 | EHF AJUBA KRAS pathway Enhancer Core transcriptional regulatory circuitry Gastroesophageal adenocarcinoma Gastric adenocarcinoma Esophageal adenocarcinoma Transcription factor Coactivator Lipid nanoparticles |
| ISSN号 | 2211-3835 |
| DOI | 10.1016/j.apsb.2024.02.025 |
| 通讯作者 | Yuan, Xiaoqing(yuanxq7@mail.sysu.edu.cn) ; Yang, Xianzhu(yangxz@scut.edu.cn) ; Yin, Dong(yind3@mail.sysu.edu.cn) |
| 英文摘要 | Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug development. However, it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors (TFs) except for the nuclear receptor family of TFs. Little is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma (GEA) or the therapeutic effects of targeting TF and transcription cofactor complexes. In this study, we found that ETS homologous factor (EHF) expression is promoted by a core transcriptional regulatory circuitry (CRC), specifically ELF3-KLF5-GATA6, and interference with its expression suppressed the malignant biological behavior of GEA cells. Importantly, we identified Ajuba LIM protein (AJUBA) as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in GEA. Furthermore, we identified KRAS signaling as a common pathway downstream of EHF and AJUBA. Applicably, dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in vivo. In conclusion, EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS pathway. Targeting of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy. |
| WOS关键词 | LIM PROTEIN AJUBA ; COREPRESSOR |
| 资助项目 | National Natural Science Foundation of China[82372617] ; National Natural Science Foundation of China[81972658] ; National Natural Science Foundation of China[81802812] ; National Natural Science Foundation of China[81803636] ; National Natural Science Foundation of China[82073067] ; National Natural Science Foundation of China[81872140] ; Guang-dong Basic and Applied Basic Research Foundation[2024B1515020090] ; Guang-dong Basic and Applied Basic Research Foundation[2023A1515012683] ; Guang-dong Basic and Applied Basic Research Foundation[2019A1515012114] ; Guang-dong Basic and Applied Basic Research Foundation[2018A030313129] ; Guang-dong Basic and Applied Basic Research Foundation[2024A1515030038] ; Guang-dong Basic and Applied Basic Research Foundation[2021A0505030084] ; Guang-dong Basic and Applied Basic Research Foundation[2019B020226003] ; Basic and Applied Basic Research of Guangzhou Municipal Basic Research Plan[2024A03J0845] ; Basic and Applied Basic Research of Guangzhou Municipal Basic Research Plan[2023A04J2098] ; National Postdoctoral Program for Innovation Talents[BX20190395] ; China Postdoctoral Science Foundation[2019M663254] ; Fundamental Research Funds for the Central Universities[20ykpy105] ; Science and Technology Planning Project of Guangdong Province[2023B1212060013] ; Science and Technology Planning Project of Guangdong Province[2020B1212030004] ; Omics Center, Sun Yat-sen Memorial Hospi-tal, Sun Yat-sen University |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001241316600001 |
| 出版者 | INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES |
| 资助机构 | National Natural Science Foundation of China ; Guang-dong Basic and Applied Basic Research Foundation ; Basic and Applied Basic Research of Guangzhou Municipal Basic Research Plan ; National Postdoctoral Program for Innovation Talents ; China Postdoctoral Science Foundation ; Fundamental Research Funds for the Central Universities ; Science and Technology Planning Project of Guangdong Province ; Omics Center, Sun Yat-sen Memorial Hospi-tal, Sun Yat-sen University |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/137128]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Yuan, Xiaoqing; Yang, Xianzhu; Yin, Dong |
| 作者单位 | 1.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Hepatobiliary Surg, Guangzhou 510120, Peoples R China 2.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Gastrointestinal Surg, Guangzhou 510120, Peoples R China 3.Chinese Acad Sci, Hefei Inst Phys Sci, Hefei 230031, Peoples R China 4.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangdong Hong Kong Joint Lab RNA Med, Guangzhou 510120, Guangdong, Peoples R China 5.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangzhou 510120, Peoples R China 6.South China Univ Technol, Sch Biomed Sci & Engn, Guangzhou Int Campus, Guangzhou 511442, Peoples R China |
| 推荐引用方式 GB/T 7714 | Peng, Li,Jiang, Yanyi,Chen, Hengxing,et al. Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma[J]. ACTA PHARMACEUTICA SINICA B,2024,14. |
| APA | Peng, Li.,Jiang, Yanyi.,Chen, Hengxing.,Wang, Yongqiang.,Lan, Qiusheng.,...&Yin, Dong.(2024).Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma.ACTA PHARMACEUTICA SINICA B,14. |
| MLA | Peng, Li,et al."Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma".ACTA PHARMACEUTICA SINICA B 14(2024). |
入库方式： OAI收割
来源：合肥物质科学研究院
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。