ArticleNature communications2023
An epigenetic switch controls an alternative NR2F2 isoform that unleashes a metastatic program in melanoma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- A truncated TNS3 isoform expressed in metastatic triple negative breast cancer stabilizes FAK and promotes lung metastasis.Oncogene · 2026Article
- Carrier-Free Berberine/Nitidine Chloride Self-Assembled Nanoparticles Induce Ferroptosis to Overcome Bortezomib Resistance in Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA Methylation-Guided Prediction and Validation of TAAD Molecular Targets.Biochemical genetics · 2026Article
- Role of NR2F2-mediated reprogramming of endothelial cells in glioblastoma progression.iScience · 2026Article
- Novel insights into extracellular vesicles: An update on biomolecules, immunomodulation and clinical strategies in skin melanoma.Clinical and translational medicine · 2026Review
- NR2F2/AGAP2 axis: regulating lipid synthesis to drive AML progression via AMPKα/ACC pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Cranial neural crest shortage leads to extensive craniofacial anomalies in mice mutant for the NR2F1/2 nuclear receptors.Developmental biology · 2026Article
- Epigenetics of Malignant Melanoma: Mechanisms, Diagnostic Approaches and Therapeutic Applications.Oncology research · 2026Review
- Integrated Single-cell Analysis Uncovers Regulatory Logic of Cranial Ectoderm Development.bioRxiv : the preprint server for biology · 2025Article
- The role of NR2F2 in cancer (Review).Oncology letters · 2025Review
- Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review).Molecular medicine reports · 2025Review
- MetFinder: A Tool for Automated Quantitation of Metastatic Burden in Histological Sections From Preclinical Models.Pigment cell & melanoma research · 2025Article
- Epigenetic regulation of mRNA mediates the phenotypic plasticity of cancer cells during metastasis and therapeutic resistance (Review).Oncology reports · 2024Review
- COUP-TFII regulates early bipotential gonad signaling and commitment to ovarian progenitors.Cell & bioscience · 2024Article
- Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics.Cancer metastasis reviews · 2023Review
- Oxidative Stress in Melanoma: Beneficial Antioxidant and Pro-Oxidant Therapeutic Strategies.Cancers · 2023Review
- Impact of the Diversity in the 5' UTR on Translation Regulation.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
Abstract
Metastatic melanoma develops once transformed melanocytic cells begin to de-differentiate into migratory and invasive melanoma cells with neural crest cell (NCC)-like and epithelial-to-mesenchymal transition (EMT)-like features. However, it is still unclear how transformed melanocytes assume a metastatic melanoma cell state. Here, we define DNA methylation changes that accompany metastatic progression in melanoma patients and discover Nuclear Receptor Subfamily 2 Group F, Member 2 - isoform 2 (NR2F2-Iso2) as an epigenetically regulated metastasis driver. NR2F2-Iso2 is transcribed from an alternative transcriptional start site (TSS) and it is truncated at the N-terminal end which encodes the NR2F2 DNA-binding domain. We find that NR2F2-Iso2 expression is turned off by DNA methylation when NCCs differentiate into melanocytes. Conversely, this process is reversed during metastatic melanoma progression, when NR2F2-Iso2 becomes increasingly hypomethylated and re-expressed. Our functional and molecular studies suggest that NR2F2-Iso2 drives metastatic melanoma progression by modulating the activity of full-length NR2F2 (Isoform 1) over EMT- and NCC-associated target genes. Our findings indicate that DNA methylation changes play a crucial role during metastatic melanoma progression, and their control of NR2F2 activity allows transformed melanocytes to acquire NCC-like and EMT-like features. This epigenetically regulated transcriptional plasticity facilitates cell state transitions and metastatic spread.
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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 Socratic graph.