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PMID: 20714342 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis.

Cell research ·Vol. 21 ·No. 2 ·2011-02-00 ·Pages 275-89

Fu J, Qin L, He T, Qin J, Hong J, Wong J, Liao L, Xu J

Abstract

The epithelial-mesenchymal transition (EMT) converts epithelial tumor cells into invasive and metastatic cancer cells, leading to mortality in cancer patients. Although TWIST is a master regulator of EMT and metastasis for breast and other cancers, the mechanisms responsible for TWIST-mediated gene transcription remain unknown. In this study, purification and characterization of the TWIST protein complex revealed that TWIST interacts with several components of the Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex, MTA2, RbAp46, Mi2 and HDAC2, and recruits them to the proximal regions of the E-cadherin promoter for transcriptional repression. Depletion of these TWIST complex components from cancer cell lines that depend on TWIST for metastasis efficiently suppresses cell migration and invasion in culture and lung metastasis in mice. These findings not only provide novel mechanistic and functional links between TWIST and the Mi2/NuRD complex but also establish new essential roles for the components of Mi2/NuRD complex in cancer metastasis.

MeSH Terms
Animals Autoantigens/genetics,metabolism Cadherins/genetics,metabolism Cell Line Cell Movement Epithelial-Mesenchymal Transition Histone Deacetylase 2/metabolism Histone Deacetylases/genetics,metabolism Humans Mi-2 Nucleosome Remodeling and Deacetylase Complex/genetics,metabolism,physiology Mice Neoplasm Invasiveness Neoplasm Metastasis Promoter Regions, Genetic RNA Interference RNA, Small Interfering/metabolism Repressor Proteins/genetics,metabolism Retinoblastoma-Binding Protein 7/metabolism Twist-Related Protein 1/genetics,metabolism,physiology
Chemicals
Autoantigens CHD4 protein, human Cadherins RBBP7 protein, human RNA, Small Interfering Repressor Proteins Retinoblastoma-Binding Protein 7 Twist-Related Protein 1 MTA2 protein, human HDAC2 protein, human Histone Deacetylase 2 Histone Deacetylases Mi-2 Nucleosome Remodeling and Deacetylase Complex
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fu Junjiang
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Qin Li
He Tao
Qin Jun
Hong Jun
Wong Jiemin
Liao Lan
Xu Jianming
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Article Info
Journal
Cell research
Abbr.
Cell Res
ISSN
1748-7838
DOI
10.1038/cr.2010.118
Published
2011-02-00
Epub
2010-00-17
Pages
275-89
Language
English
Region
England
NLM ID
9425763
PMCID
PMC3193433
Subset
IM
Grants
NCI NIH HHS · R01 CA112403 · United States
NCI NIH HHS · R01 CA119689 · United States
NIDDK NIH HHS · R01 DK058242 · United States
NIDDK NIH HHS · U19 DK062434 · United States
External Links
PubMed source DOI: 10.1038/cr.2010.118 PMC Full Text View journal details
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