4.7 Article

Aryl hydrocarbon receptor is a tumor promoter in MYCN-amplified neuroblastoma cells through suppression of differentiation

期刊

ISCIENCE
卷 26, 期 11, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.isci.2023.108303

关键词

-

向作者/读者索取更多资源

This study identifies the aryl hydrocarbon receptor (AhR) as a transcription factor promoting the growth and suppressing the differentiation of MYCN-amplified neuroblastoma. AhR antagonism, combined with retinoic acid, may result in a more durable response in patients.
Neuroblastoma is the most common extracranial solid tumor in children. MYCN amplification is detected in almost half of high-risk cases and is associated with poorly differentiated tumors, poor patient prognosis and poor response to therapy, including retinoids. We identify the aryl hydrocarbon receptor (AhR) as a transcription factor promoting the growth and suppressing the differentiation of MYCN-amplified neuroblastoma. A neuroblastoma specific AhR transcriptional signature reveals an inverse correlation of AhR activity with patients' outcome, suggesting AhR activity is critical for disease progression. AhR modulates chromatin structures, reducing accessibility to regions responsive to retinoic acid. Genetic and pharmacological inhibition of AhR results in induction of differentiation. Importantly, AhR antagonism with clofazimine synergizes with retinoic acid in inducing differentiation both in vitro and in vivo. Thus, we propose AhR as a target for MYCN-amplified neuroblastoma and that its antagonism, combined with current standard-of-care, may result in a more durable response in patients.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据