title: LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Chen
authors.forename: Yimin
authors.initials: Y
authors.lastname: Sun
authors.forename: Fen
authors.initials: F
authors.lastname: Yang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.forename: Luyang
authors.initials: L
authors.lastname: Sun
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Ruifang
authors.initials: R
authors.lastname: Li
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Yi
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
mesh_terms: 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
chemical_list: 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