LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer.
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 TGFbeta1 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 TGFbeta1. 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.
Wang
Yan
Y
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
Zhang
Hua
H
Chen
Yupeng
Y
Sun
Yimin
Y
Yang
Fen
F
Yu
Wenhua
W
Liang
Jing
J
Sun
Luyang
L
Yang
Xiaohan
X
Shi
Lei
L
Li
Ruifang
R
Li
Yanyan
Y
Zhang
Yu
Y
Li
Qian
Q
Yi
Xia
X
Shang
Yongfeng
Y
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D056466:Histone Demethylases; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000235:genetics*; D009368:Neoplasm Transplantation; D009707:Nucleosomes / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D009707:Nucleosomes; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; C464671:transforming growth factor beta1 (41-65); D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex