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Updated: Jun 10, 2026

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis
1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
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.
Insights
TWIST protein interacts with the Mi2/NuRD complex to drive cancer metastasis. Suppressing these interactions halts cancer cell invasion and spread, offering new therapeutic targets for metastasis.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- The epithelial-mesenchymal transition (EMT) is crucial for cancer cell invasion and metastasis.
- TWIST is a key regulator of EMT and metastasis in various cancers.
- The precise mechanisms of TWIST-mediated gene transcription in metastasis are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying TWIST-mediated gene transcription.
- To investigate the interaction between TWIST and other protein complexes in cancer metastasis.
- To identify potential therapeutic targets for inhibiting cancer metastasis.
Main Methods:
- Purification and characterization of the TWIST protein complex.
- Co-immunoprecipitation assays to identify interacting proteins.
- Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) to assess promoter binding.
- In vitro cell migration and invasion assays.
- In vivo mouse models of lung metastasis.
Main Results:
- TWIST interacts with components of the Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex, including MTA2, RbAp46, Mi2, and HDAC2.
- The TWIST-Mi2/NuRD complex is recruited to the E-cadherin promoter, leading to transcriptional repression.
- Depletion of TWIST complex components significantly suppresses cancer cell migration, invasion, and lung metastasis in mice.
Conclusions:
- TWIST functions by recruiting the Mi2/NuRD complex to target gene promoters, thereby regulating genes critical for metastasis.
- The Mi2/NuRD complex plays an essential role in TWIST-driven cancer metastasis.
- Targeting the TWIST-Mi2/NuRD interaction presents a potential therapeutic strategy for combating cancer metastasis.
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