1. Academic Validation
  2. Transcriptional factor BRD4 promotes the stemness of esophageal cancer by activating the nuclear PD-L1/RelB axis

Transcriptional factor BRD4 promotes the stemness of esophageal cancer by activating the nuclear PD-L1/RelB axis

  • Environ Toxicol. 2023 Aug 24. doi: 10.1002/tox.23939.
Shouguo Li 1 Qunhuang Guo 1 Ruixiang Guo 1 Hui Xu 1
Affiliations

Affiliation

  • 1 Department of Tumor Radiotherapy, Zhongshan Hospital, Xiamen University, Xiamen, China.
Abstract

Esophageal Cancer (EC) is a prevalent malignancy associated with therapeutic resistance and poor prognosis. This study investigates the role of programmed death-ligand 1 (PD-L1) in esophageal Cancer stem cell (ECSC) formation. ECSCs were enriched and characterized using various assays. We found that both PD-L1 and bromodomain-containing protein 4 (BRD4) were upregulated in ECSCs, promoting their stemness. Inhibiting BRD4 suppressed ECSC markers expression and sphere formation. Furthermore, BRD4 inhibitors downregulated membrane and nuclear PD-L1 levels, with knockdown of PD-L1 inhibiting ECSC formation. PD-L1 degraders also affected PD-L1 and its downstream effector RelB expression. Moreover, inhibiting RelB influenced sphere formation through interleukin-6 expression. This study reveals the critical role of the BRD4/nuclear PD-L1/RelB axis in ECSC formation, highlighting nuclear PD-L1 as a potential immunotherapeutic target for refractory EC.

Keywords

RelB; bromodomain-containing protein 4; cancer stem cell; esophageal cancer; programmed death-ligand 1; stemness.

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