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

Yan Wang, Hua Zhang, Yupeng Chen, Yimin Sun, Fen Yang, Wenhua Yu, Jing Liang, Luyang Sun, Xiaohan Yang, Lei Shi, Ruifang Li, Yanyan Li, Yu Zhang, Qian Li, Xia Yi, Yongfeng Shang

Research output: Contribution to journalArticle

407 Citations (Scopus)

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 TGFβ1 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 TGFβ1. 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.

Original languageEnglish (US)
Pages (from-to)660-672
Number of pages13
JournalCell
Volume138
Issue number4
DOIs
StatePublished - Aug 21 2009

Fingerprint

Mi-2 Nucleosome Remodeling and Deacetylase Complex
Lysine
Breast Neoplasms
Neoplasm Metastasis
Chromatin Assembly and Disassembly
Chromatin
Histone Demethylases
Cell signaling
Histone Deacetylases
Epithelial-Mesenchymal Transition
Cell proliferation
Histones
Adenosine Triphosphatases
Cell Survival
Animals
Down-Regulation
Cells
Cell Proliferation

Keywords

  • HUMDISEASE
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

LSD1 Is a Subunit of the NuRD Complex and Targets the Metastasis Programs in Breast Cancer. / Wang, Yan; Zhang, Hua; Chen, Yupeng; Sun, Yimin; Yang, Fen; Yu, Wenhua; Liang, Jing; Sun, Luyang; Yang, Xiaohan; Shi, Lei; Li, Ruifang; Li, Yanyan; Zhang, Yu; Li, Qian; Yi, Xia; Shang, Yongfeng.

In: Cell, Vol. 138, No. 4, 21.08.2009, p. 660-672.

Research output: Contribution to journalArticle

Wang, Y, Zhang, H, Chen, Y, Sun, Y, Yang, F, Yu, W, Liang, J, Sun, L, Yang, X, Shi, L, Li, R, Li, Y, Zhang, Y, Li, Q, Yi, X & Shang, Y 2009, 'LSD1 Is a Subunit of the NuRD Complex and Targets the Metastasis Programs in Breast Cancer', Cell, vol. 138, no. 4, pp. 660-672. https://doi.org/10.1016/j.cell.2009.05.050
Wang, Yan ; Zhang, Hua ; Chen, Yupeng ; Sun, Yimin ; Yang, Fen ; Yu, Wenhua ; Liang, Jing ; Sun, Luyang ; Yang, Xiaohan ; Shi, Lei ; Li, Ruifang ; Li, Yanyan ; Zhang, Yu ; Li, Qian ; Yi, Xia ; Shang, Yongfeng. / LSD1 Is a Subunit of the NuRD Complex and Targets the Metastasis Programs in Breast Cancer. In: Cell. 2009 ; Vol. 138, No. 4. pp. 660-672.
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