[HTML][HTML] LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer

Y Wang, H Zhang, Y Chen, Y Sun, F Yang, W Yu… - Cell, 2009 - cell.com
Y Wang, H Zhang, Y Chen, Y Sun, F Yang, W Yu, J Liang, L Sun, X Yang, L Shi, R Li, Y Li
Cell, 2009cell.com
Summary 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 …
Summary
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.
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