在管腔型乳腺癌中，CHD4通过TRPS1介导SOX2转录。

CHD4 mediates SOX2 transcription through TRPS1 in luminal breast cancer.

作者信息

Zhang Jun, Lv Xiang, Wei Bo, Gong Xue, Chen Liming

机构信息

Department of Biochemistry, School of Life Sciences, Nanjing Normal University, Nanjing, China.

Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Cell Signal. 2022 Dec;100:110464. doi: 10.1016/j.cellsig.2022.110464. Epub 2022 Sep 6.

DOI:10.1016/j.cellsig.2022.110464

PMID:36075559

Abstract

Chromodomain helicase DNA binding protein 4 (CHD4), as a core component of the nucleosome remodeling and deactetylase (NuRD) complex, participated in the inititation and development of myriad cancers. However, little is known about the linkage between CHD4 and breast cancer stemness. Here, we found that CHD4 repress the expression of SOX2, a key regulator of cancer stem cells (CSCs), to suppress cancer stemness in breast cancer. Mechanistically, CHD4 binds to the promoter of SOX2 depend on TRPS1. And CHD4 transcriptional activation of SOX2 was abolished by TRPS1. These findings identify CHD4 as a regulator of SOX2 linked to breast cancer stemness and provide detailed mechanistic of CHD4 in CSC functions.

摘要

染色质结构域解旋酶DNA结合蛋白4（CHD4）作为核小体重塑与去乙酰化酶（NuRD）复合物的核心成分，参与了多种癌症的发生和发展。然而，关于CHD4与乳腺癌干性之间的联系却知之甚少。在此，我们发现CHD4通过抑制癌症干细胞（CSC）的关键调节因子SOX2的表达来抑制乳腺癌的癌症干性。机制上，CHD4依赖TRPS1与SOX2的启动子结合。并且TRPS1消除了CHD4对SOX2的转录激活作用。这些发现确定CHD4是与乳腺癌干性相关的SOX2的调节因子，并提供了CHD4在CSC功能中的详细机制。