ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-β-Induced EMT and Cancer Metastasis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Decoding epithelial-mesenchymal transitions with multi-omics.Nature reviews. Genetics · 2026Review
- RAB4A acts as a negative feedback regulator of extracellular vesicle secretion during TGF-β signaling.The FEBS journal · 2026Article
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- Integrative Transcriptional and Chromatin Analyses Reveal Enhancer-Mediated Regulatory Programs Driving Breast Cancer Metastasis.Molecular cancer research : MCR · 2026Article
- TGFβ signaling promotes cell cycle progression and resistance to the CDK4/6 inhibitor palbociclib through SOX4 transcriptional modulation in breast cancer cells.Cell death & disease · 2026Article
- A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure.Nature cardiovascular research · 2026Article
- The long noncoding RNA VIM-AS1 and nucleoporin Nup358/RanBP2 regulate SMAD nuclear accumulation during TGF-β signaling.Nucleic acids research · 2026Article
- CellMiner cross-database (CellMinerCDB) version 2.2 for explorations of patient-derived cancer cell line pharmacogenomics.Nucleic acids research · 2026Article
- Dynamic three-dimensional chromatin remodeling in lung disease: mechanistic principles, pathogenic regulatory networks, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- The role of TEAD4 gene in the Hippo signaling pathway in triple-negative breast cancer and targeted therapy strategies.BMC medical genomics · 2025Article
- Identification of a Distal Enhancer That Regulates TGF-β-Induced SNAI1 Expression.Cancer science · 2025Article
- Distinct BMP-Smad signaling outputs confer diverse functions in dental mesenchyme.Development (Cambridge, England) · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Regulating epithelial-mesenchymal plasticity from 3D genome organization.Communications biology · 2024Review
- Switch of ELF3 and ATF4 transcriptional axis programs the amino acid insufficiency-linked epithelial-to-mesenchymal transition.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- FOXA2 Suppression by TRIM36 Exerts Anti-Tumor Role in Colorectal Cancer Via Inducing NRF2/GPX4-Regulated Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Recapitulation of patient-specific 3D chromatin conformation using machine learning.Cell reports methods · 2023Article
- Heterogeneity and plasticity of epithelial-mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms.Cell proliferation · 2023Review
- Expression of EMT-related genes in lymph node metastasis in endometrial cancer: a TCGA-based study.World journal of surgical oncology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription growth factor β (TGF-β) signaling-triggered epithelial-to-mesenchymal transition (EMT) process is associated with tumor stemness, metastasis, and chemotherapy resistance. However, the epigenomic basis for TGF-β-induced EMT remains largely unknown. Here we reveal that HDAC1-mediated global histone deacetylation and the gain of specific histone H3 lysine 27 acetylation (H3K27ac)-marked enhancers are essential for the TGF-β-induced EMT process. Enhancers gained upon TGF-β treatment are linked to gene activation of EMT markers and cancer metastasis. Notably, dynamic enhancer gain or loss mainly occurs within pre-existing topologically associated domains (TADs) in epithelial cells, with minimal three-dimensional (3D) genome architecture reorganization. Through motif enrichment analysis of enhancers that are lost or gained upon TGF-β stimulation, we identify FOXA2 as a key factor to activate epithelial-specific enhancer activity, and we also find that TEAD4 forms a complex with SMAD2/3 to mediate TGF-β signaling-triggered mesenchymal enhancer reprogramming. Together, our results implicate that key transcription-factor (TF)-mediated enhancer reprogramming modulates the developmental transition in TGF-β signaling-associated cancer metastasis.
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Registered trials
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.