Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer
文献类型：期刊论文
| 作者 | Wang, Xiaomin1,2; Xu, Jun1,2; Sun, Yiming1; Cao, Siyuwei1; Zeng, Hanlin1; Jin, Nan1; Shou, Matthew4; Tang, Shuai1; Chen, Yi1,2 ; Huang, Min1,2,3
|
| 刊名 | ACTA PHARMACEUTICA SINICA B
 |
| 出版日期 | 2023-06-01 |
| 卷号 | 13期号:6页码:2601-2612 |
| 关键词 | HDAC inhibitors Drug resistance Histone methylation Histone acetylation Epigenetic interplay Hedgehog pathway ZIC1 LIFR Combination therapy Breast cancer |
| ISSN号 | 2211-3835 |
| DOI | 10.1016/j.apsb.2023.03.009 |
| 通讯作者 | Chen, Yi(mhuang@simm.ac.cn) ; Huang, Min(ychen@simm.ac.cn) |
| 英文摘要 | Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local inter-play between different histone marks, leading to a switch of transcriptional outcome and therapeutic re-sponses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnera-bility of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC. 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| WOS关键词 | DEACETYLASE INHIBITOR ; EZH2 ; METHYLATION ; ACTIVATION ; REPRESSION ; SUZ12 ; GLI2 |
| 资助项目 | National Natural Science Foun- dation of China[82225046] ; National Natural Science Foun- dation of China[81821005] ; National Natural Science Foun- dation of China[81903640] ; Program of Shanghai Academic Research Leader[20XD1424800] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001027048900001 |
| 出版者 | INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306445]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Yi; Huang, Min |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Canc Res Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 4.Vanderbilt Univ Sch Med, Dept Mol Physiol & Biophys, Div Diabet Endocrinol & Metab, Nashville, TN 37232 USA |
| 推荐引用方式 GB/T 7714 | Wang, Xiaomin,Xu, Jun,Sun, Yiming,et al. Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer[J]. ACTA PHARMACEUTICA SINICA B,2023,13(6):2601-2612. |
| APA | Wang, Xiaomin.,Xu, Jun.,Sun, Yiming.,Cao, Siyuwei.,Zeng, Hanlin.,...&Huang, Min.(2023).Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer.ACTA PHARMACEUTICA SINICA B,13(6),2601-2612. |
| MLA | Wang, Xiaomin,et al."Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer".ACTA PHARMACEUTICA SINICA B 13.6(2023):2601-2612. |
入库方式： OAI收割
来源：上海药物研究所
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。