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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Josh Haipeng Lei
  • Lei Zhang
  • Zhenyi Wang
  • Raoul Peltier
  • Ganchao Chen
  • Shiqi Lin
  • Kai Miao
  • Chu-Xia Deng

Detail(s)

Original languageEnglish
Article number861221
Journal / PublicationFrontiers in Immunology
Volume13
Online published25 Apr 2022
Publication statusPublished - Apr 2022

Link(s)

Abstract

Epigenetic 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.

Research Area(s)

  • BRD4, epigenetic, FGFR2, immunotherapy, posttranslational modifications, TNBC

Citation Format(s)

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 Haipeng; Zhang, Lei; Wang, Zhenyi et al.
In: Frontiers in Immunology, Vol. 13, 861221, 04.2022.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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