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Updated: Jul 17, 2025

Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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Molecular mechanisms of TWIST1-regulated transcription in EMT and cancer metastasis

Xiaobin Yu1, Tao He1, Zhangwei Tong1

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.

EMBO Reports
|September 8, 2023
PubMed

Insights

TWIST1 acetylation controls its function in cancer metastasis. Diacetylation of TWIST1-K73/76 recruits TIP60-Com to activate mesenchymal genes, while non-acetylation recruits NuRD to repress epithelial genes.

Area of Science:

  • Molecular biology
  • Cancer research
  • Epigenetics

Background:

  • TWIST1 is a key regulator of epithelial-to-mesenchymal transition (EMT), a process critical for cancer metastasis.
  • The precise mechanisms governing TWIST1's transcriptional activation or repression functions remain incompletely understood.

Purpose of the Study:

  • To elucidate how TWIST1's N-terminus influences its transcriptional activity and role in cancer progression.
  • To investigate the role of TWIST1 acetylation status in mediating interactions with chromatin-modifying complexes.

Main Methods:

  • Investigated TWIST1 interactions with NuRD and TIP60 complexes using biochemical assays.
  • Analyzed the impact of TWIST1 acetylation at K73/76 on gene expression and cancer metastasis.
  • Utilized BRD8 knockdown to assess its role in TWIST1-mediated transcriptional regulation.

Main Results:

  • TWIST1's N-terminus modulates gene expression, cancer growth, and metastasis.
  • Non-acetylated TWIST1-K73/76 interacts with NuRD to repress epithelial genes.
  • Diacetylated TWIST1-acK73/76 binds BRD8 and recruits TIP60-Com to activate mesenchymal genes and MYC.
  • BRD8 knockdown disrupts TWIST1/TIP60-Com interaction, reducing metastasis.

Conclusions:

  • TWIST1 acetylation status dictates its interaction with NuRD or TIP60-Com, thereby controlling target gene expression.
  • Both TWIST1/NuRD and TWIST1/TIP60-Com complexes are essential for TWIST1's pro-metastatic functions.
  • Targeting BRD8 presents a potential strategy to inhibit TWIST1-driven gene expression and metastasis.
Keywords:
BRD8NuRDTIP60TWIST1acetylationepithelial-to-mesenchymal transition

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