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

doi:10.1016/j.cell.2009.05.050

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 journal › Article › peer-review

580 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 language	English (US)
Pages (from-to)	660-672
Number of pages	13
Journal	Cell
Volume	138
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2009.05.050
State	Published - Aug 21 2009

Keywords

HUMDISEASE
PROTEINS
SIGNALING

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2009.05.050

Cite this

@article{76649c02e4c540a3b06affc34fb6386a,

title = "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 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.",

keywords = "HUMDISEASE, PROTEINS, SIGNALING",

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

note = "Funding Information: We thank Joanne Balmer Green (Penn State University) for editorial assistance. This work was supported by grants (30830032, 30621002 and 30470912, to Y.S.) from the National Natural Science Foundation of China and grants (863 Program: 2006AA02Z466 and 973 Program: 2005CB522404 and 2007CB914503, to Y.S.) from the Ministry of Science and Technology of China. ",

year = "2009",

month = aug,

day = "21",

doi = "10.1016/j.cell.2009.05.050",

language = "English (US)",

volume = "138",

pages = "660--672",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - LSD1 Is a Subunit of the NuRD Complex and Targets the Metastasis Programs in Breast Cancer

AU - Wang, Yan

AU - Zhang, Hua

AU - Chen, Yupeng

AU - Sun, Yimin

AU - Yang, Fen

AU - Yu, Wenhua

AU - Liang, Jing

AU - Sun, Luyang

AU - Yang, Xiaohan

AU - Shi, Lei

AU - Li, Ruifang

AU - Li, Yanyan

AU - Zhang, Yu

AU - Li, Qian

AU - Yi, Xia

AU - Shang, Yongfeng

N1 - Funding Information: We thank Joanne Balmer Green (Penn State University) for editorial assistance. This work was supported by grants (30830032, 30621002 and 30470912, to Y.S.) from the National Natural Science Foundation of China and grants (863 Program: 2006AA02Z466 and 973 Program: 2005CB522404 and 2007CB914503, to Y.S.) from the Ministry of Science and Technology of China.

PY - 2009/8/21

Y1 - 2009/8/21

N2 - 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.

AB - 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.

KW - HUMDISEASE

KW - PROTEINS

KW - SIGNALING

UR - http://www.scopus.com/inward/record.url?scp=68749108259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68749108259&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2009.05.050

DO - 10.1016/j.cell.2009.05.050

M3 - Article

C2 - 19703393

AN - SCOPUS:68749108259

SN - 0092-8674

VL - 138

SP - 660

EP - 672

JO - Cell

JF - Cell

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this