UM  > Faculty of Health Sciences
Affiliated with RCfalse
Status已發表Published
FGFR2–BRD4 Axis Regulates Transcriptional Networks of Histone 3 Modification and Synergy Between Its Inhibitors and PD-1/PD-L1 in a TNBC Mouse Model
Lei, Josh Haipeng1,2,3; Zhang, Lei1,4; Wang, Zhenyi5; Peltier, Raoul3; Xie, Yusheng3,6; Chen, Ganchao3; Lin, Shiqi1,2; Miao, Kai1,2; Deng, Chu Xia1,2; Sun, Hongyan3,7
2022-04-25
Source PublicationFrontiers in Immunology
Volume13
AbstractEpigenetic reprogramming is an independent mode of gene expression that often involves changes in the transcription and chromatin structure due to tumor initiation and development. In this study, we developed a specifically modified peptide array and searched for a recognized epigenetic reader. Our results demonstrated that BRD4 is not only an acetylation reader but of propionylation as well. We also studied the quantitative binding affinities between modified peptides and epigenetic regulators by isothermal titration calorimetry (ITC). Furthermore, we introduced the Fgfr2-S252W transgenic mouse model to confirm that this acetylation is associated with the activation of c-Myc and drives tumor formation. Targeted disruption of BRD4 in Fgfr2-S252W mouse tumor cells also confirmed that BRD4 is a key regulator of histone 3 acetylation. Finally, we developed a tumor slice culture system and demonstrated the synergy between immune checkpoint blockade and targeted therapy in triple-negative breast cancer (TNBC). These data extend our understanding of epigenetic reprogramming and epigenetics-based therapies.
KeywordBRD4 epigenetic FGFR2 immunotherapy posttranslational modifications TNBC
DOI10.3389/fimmu.2022.861221
URLView the original
Language英語English
Scopus ID2-s2.0-85129836816
Fulltext Access
Citation statistics
Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
DEPARTMENT OF BIOMEDICAL SCIENCES
Affiliation1.Cancer Center, Faculty of Health Sciences, University of Macau, Macao
2.Ministry of Education, Frontier Science Centre for Precision Oncology, University of Macau, Taipa, Macao
3.Department of Chemistry, City University of Hong Kong, Kowloon, Hong Kong
4.Department of Vascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
5.Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Heifei, China
6.Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China
7.Key Laboratory of Biochip Technology, Biotech and Health Centre, City University of Hong Kong, Shenzhen Research Institute, Shenzhen, China
First Author AffilicationCancer Centre;  University of Macau
Recommended Citation
GB/T 7714
Lei, Josh Haipeng,Zhang, Lei,Wang, Zhenyi,et al. FGFR2–BRD4 Axis Regulates Transcriptional Networks of Histone 3 Modification and Synergy Between Its Inhibitors and PD-1/PD-L1 in a TNBC Mouse Model[J]. Frontiers in Immunology,2022,13.
APA Lei, Josh Haipeng,Zhang, Lei,Wang, Zhenyi,Peltier, Raoul,Xie, Yusheng,Chen, Ganchao,Lin, Shiqi,Miao, Kai,Deng, Chu Xia,&Sun, Hongyan.(2022).FGFR2–BRD4 Axis Regulates Transcriptional Networks of Histone 3 Modification and Synergy Between Its Inhibitors and PD-1/PD-L1 in a TNBC Mouse Model.Frontiers in Immunology,13.
MLA Lei, Josh Haipeng,et al."FGFR2–BRD4 Axis Regulates Transcriptional Networks of Histone 3 Modification and Synergy Between Its Inhibitors and PD-1/PD-L1 in a TNBC Mouse Model".Frontiers in Immunology 13(2022).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Lei, Josh Haipeng]'s Articles
[Zhang, Lei]'s Articles
[Wang, Zhenyi]'s Articles
Baidu academic
Similar articles in Baidu academic
[Lei, Josh Haipeng]'s Articles
[Zhang, Lei]'s Articles
[Wang, Zhenyi]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Lei, Josh Haipeng]'s Articles
[Zhang, Lei]'s Articles
[Wang, Zhenyi]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.