LSD1 Is a Subunit of the NuRD Complex and Targets the Metastasis Programs in Breast Cancer

被引：579

作者：

Wang, Yan ^{[1
]}

Zhang, Hua ^{[1
]}

Chen, Yupeng ^{[1
]}

Sun, Yimin ^{[1
]}

Yang, Fen ^{[1
]}

Yu, Wenhua ^{[1
]}

Liang, Jing ^{[1
]}

Sun, Luyang ^{[1
]}

Yang, Xiaohan ^{[1
]}

Shi, Lei ^{[1
]}

Li, Ruifang ^{[1
]}

Li, Yanyan ^{[1
]}

Zhang, Yu ^{[1
]}

Li, Qian ^{[1
]}

Yi, Xia ^{[1
]}

Shang, Yongfeng ^{[1
]}

机构：

[1] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100191, Peoples R China

来源：

CELL | 2009年 / 138卷 / 04期

基金：

中国国家自然科学基金;

关键词：

RECEPTOR-REGULATED TRANSCRIPTION; HISTONE LYSINE DEMETHYLASES; TGF-BETA; ENDOMETRIAL CARCINOGENESIS; MESENCHYMAL TRANSITIONS; MOLECULAR-MECHANISMS; MI-2/NURD COMPLEX; GENE-REGULATION; EMERGING ROLES; ESTROGEN;

D O I：

10.1016/j.cell.2009.05.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lysine-specific demethylase 1 (LSD1) exerts pathway-specific activity in animal development and has been linked to several high-risk cancers. Here, we report that LSD1 is an integral component of the Mi-2/nucleosome remodeling and deacetylase (NuRD) complex. Transcriptional target analysis revealed that the LSD1/NuRD complexes regulate several cellular signaling pathways including TGF beta 1 signaling pathway that are critically involved in cell proliferation, survival, and epithelial-to-mesenchymal transition. We demonstrated that LSD1 inhibits the invasion of breast cancer cells in vitro and suppresses breast cancer metastatic potential in vivo. We found that LSD1 is downregulated in breast carcinomas and that its level of expression is negatively correlated with that of TGFb1. Our data provide a molecular basis for the interplay of histone demethylation and deacetylation in chromatin remodeling. By enlisting LSD1, the NuRD complex expands its chromatin remodeling capacity to include ATPase, histone deacetylase, and histone demethylase.

引用

页码：660 / 672

页数：13

共 44 条

[1] Mi-2/NuRD: multiple complexes for many purposes [J].