ArticleOncogene2017
Twist1 promotes breast cancer invasion and metastasis by silencing Foxa1 expression.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
- Prognostic and clinicopathological value of Twist expression in breast cancer: A meta-analysis.PloS one · 2017Pooled it
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- Phosphorylation-dependent modulation of the Lamin A/C-EZH2 complex regulates epithelial-mesenchymal plasticity.Nucleic acids research · 2026Article
- Twist1 silencing suppresses triple-negative breast cancer progression by reducing RNF40 transcription.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Deubiquitinating enzyme USP42 promotes breast cancer progression by inhibiting JNK/p38-mediated apoptosis.Scientific reports · 2025Article
- Suppression of breast cancer metastatic behavior by microRNAs targeting EMT transcription factors. A relevant participation of miR-196a-5p and miR-22-3p in ZEB1 expression.Breast cancer research and treatment · 2025Article
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- Benzophenone-3 alters expression of genes encoding vascularization and epithelial-mesenchymal transition functions during Trp53-null mammary tumorigenesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2024Article
- Integrative analysis of chromatin accessibility and transcriptome landscapes in the induction of peritoneal fibrosis by high glucose.Journal of translational medicine · 2024Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with poor prognosis owing to its role in promoting epithelial-to-mesenchymal transition (EMT), invasiveness and metastasis. However, the regulatory and functional relationships between Twist1 and Foxa1 in breast cancer progression are unknown. In this study, we demonstrate that in the estrogen receptor (ERα)-positive LBC cells Twist1 silences Foxa1 expression, which has an essential role in relieving Foxa1-arrested migration, invasion and metastasis of breast cancer cells. Mechanistically, Twist1 binds to Foxa1 proximal promoter and recruits the NuRD transcriptional repressor complex to de-acetylate H3K9 and repress RNA polymerase II recruitment. Twist1 also silences Foxa1 promoter by inhibiting AP-1 recruitment. Twist1 expression in MCF7 cells silenced Foxa1 expression, which was concurrent with the induction of EMT, migration, invasion and metastasis of these cells. Importantly, restored Foxa1 expression in these cells largely inhibited Twist1-promoted migration, invasion and metastasis. Restored Foxa1 expression did not change the Twist1-induced mesenchymal cellular morphology and the expression of Twist1-regulated E-cadherin, β-catenin, vimentin and Slug, but it partially rescued Twist1-silenced ERα and cytokeratin 8 expression and reduced Twist1-induced integrin α5, integrin β1 and MMP9 expression. In a xenografted mouse model, restored Foxa1 also increased Twist1-repressed LBC markers and decreased Twist1-induced BLBC markers. Furthermore, Twist1 expression is negatively correlated with Foxa1 in the human breast tumors. The tumors with high Twist1 and low Foxa1 expressions are associated with poor distant metastasis-free survival. These results demonstrate that Twist1's silencing effect on Foxa1 expression is largely responsible for Twist1-induced migration, invasion and metastasis, but less responsible for Twist1-induced mesenchymal morphogenesis and expression of certain EMT markers.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.