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: 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
• Journal: Cell (Cell) Vol. 138 Issue 4 Pg. 660-72 (Aug 21 2009) ISSN: 1097-4172 [Electronic] United States
• PMID: 19703393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nucleosomes
• Peptide Fragments
• Transforming Growth Factor beta1
• transforming growth factor beta1 (41-65)
• Histone Demethylases
• KDM1A protein, human
• Oxidoreductases, N-Demethylating
• Histone Deacetylases
• Mi-2 Nucleosome Remodeling and Deacetylase Complex

Topics

• Animals
• Breast Neoplasms (metabolism)
• Cell Line, Tumor
• Chromatin Assembly and Disassembly
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• HeLa Cells
• Histone Deacetylases (metabolism)
• Histone Demethylases
• Humans
• Mi-2 Nucleosome Remodeling and Deacetylase Complex
• Mice
• Mice, SCID
• Neoplasm Metastasis (genetics)
• Neoplasm Transplantation
• Nucleosomes (metabolism)
• Oxidoreductases, N-Demethylating (chemistry, metabolism)
• Peptide Fragments (metabolism)
• Transforming Growth Factor beta1 (metabolism)