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

433 Scopus citations

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

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Keywords

  • HUMDISEASE
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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, 138(4), 660-672. https://doi.org/10.1016/j.cell.2009.05.050