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.

Cell
|August 26, 2009
PubMed

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.

Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...