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Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer
Yan Wang1, Hua Zhang, Yupeng Chen
1Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
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.
Insights
Lysine-specific demethylase 1 (LSD1) is part of the NuRD complex, regulating cell pathways and inhibiting breast cancer invasion. LSD1 is downregulated in breast cancer, correlating with increased TGFbeta1 signaling.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- Lysine-specific demethylase 1 (LSD1) plays a role in development and cancer.
- The Mi-2/nucleosome remodeling and deacetylase (NuRD) complex is involved in gene regulation.
- Understanding the interplay between histone modification complexes is crucial for cancer research.
Purpose of the Study:
- To investigate the role of LSD1 within the NuRD complex.
- To determine the functional impact of LSD1/NuRD on cellular signaling pathways, particularly in breast cancer.
- To explore the correlation between LSD1 expression and breast cancer progression.
Main Methods:
- Transcriptional target analysis to identify regulated pathways.
- In vitro assays to assess breast cancer cell invasion.
- In vivo studies to evaluate metastatic potential.
- Immunohistochemical analysis of LSD1 expression in breast carcinomas.
Main Results:
- LSD1 was identified as an integral component of the NuRD complex.
- The LSD1/NuRD complex regulates TGFbeta1 signaling, impacting cell proliferation, survival, and epithelial-to-mesenchymal transition.
- LSD1 inhibited breast cancer cell invasion in vitro and suppressed metastatic potential in vivo.
- LSD1 expression was downregulated in breast carcinomas and negatively correlated with TGFbeta1 levels.
Conclusions:
- LSD1's integration into the NuRD complex expands its chromatin remodeling capabilities.
- The LSD1/NuRD complex plays a significant role in suppressing breast cancer metastasis.
- Downregulation of LSD1 in breast cancer may contribute to tumor progression via TGFbeta1 signaling.
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