Volume 21, No 2, Feb 2011
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 21 Issue 2, February 2011: 275-289
ORIGINAL ARTICLES
The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis
Junjiang Fu1, Li Qin1, Tao He1,2, Jun Qin1, Jun Hong1, Jiemin Wong3, Lan Liao1 and Jianming Xu1,2,3
1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
2Luzhou Medical College, Luzhou, Sichuan 646000, China
3Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China
Correspondence: Jianming Xu,(jxu@bcm.edu)
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.
Cell Research (2011) 21: 275-289. doi:10.1038/cr.2010.118; published online 17 August 2010
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