ArticleCancer research2022
NR2F1 Is a Barrier to Dissemination of Early-Stage Breast Cancer Cells.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- Regulating the dormancy of cancer stem cells: a novel approach to preventing cancer relapse.Cell death & disease · 2026Review
- Glucocorticoid-Induced Proteome and Phosphoproteome Changes in Breast Cancer Cell Lines.Journal of proteome research · 2026Article
- Gene regulatory network transitions reveal the central transcription factors in lung adenocarcinoma progression.NPJ systems biology and applications · 2026Article
- Circulating tumor cells as predictive biomarkers in the risk stratification of DCIS: Evidence of early dissemination.Science advances · 2025Article
- Elevated NR2F1 underlies the persistence of invasive disease after treatment of BRAF-mutant melanoma.The Journal of clinical investigation · 2025Article
- Autophagy-induced NR2F1 activation promotes the apoptosis of lens epithelial cells and facilitates cataract-associated fibrosis through targeting STAT3.Genes & diseases · 2025Article
- Heterogeneous graph contrastive learning for integration and alignment of spatial transcriptomics data.Briefings in bioinformatics · 2025Article
- Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications.Cancer cell · 2025Review
- Antitumor CD4+ T Helper 1 Cells Target and Control the Outgrowth of Disseminated Cancer Cells.Cancer immunology research · 2025Article
- Re-epithelialization of cancer cells increases autophagy and DNA damage: Implications for breast cancer dormancy and relapse.Science signaling · 2025Article
- Sleepyhead, deadly awakening: the dynamics of metastatic organotropism, tumor dormancy and therapeutic implications.Frontiers in oncology · 2025Review
- Integrated multi-omics analysis reveals the immunotherapeutic significance of tumor cells with high FN1 expression in ovarian cancer.Frontiers in molecular biosciences · 2025Article
- Unraveling the Mystery of Breast Cancer Dormancy: Insights into Genetic, Receptor, and Cellular Interactions Driving Late Recurrence.Frontiers in immunology · 2025Review
- Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4.Cell communication and signaling : CCS · 2024Article
- Exosome-delivered NR2F1-AS1 and NR2F1 drive phenotypic transition from dormancy to proliferation in treatment-resistant prostate cancer via stabilizing hormonal receptors.Journal of nanobiotechnology · 2024Article
- How much do we know about the metastatic process?Clinical & experimental metastasis · 2024Review
- Unveiling cancer dormancy: Intrinsic mechanisms and extrinsic forces.Cancer letters · 2024Review
- Transcriptional regulation of genetic variants in theThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- mTOR pathway occupies a central role in the emergence of latent cancer cells.Cell death & disease · 2024Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer cells can disseminate during very early and sometimes asymptomatic stages of tumor progression. Though biological barriers to tumorigenesis have been identified and characterized, the mechanisms that limit early dissemination remain largely unknown. We report here that the orphan nuclear receptor nuclear receptor subfamily 2, group F, member 1 (NR2F1)/COUP-TF1 serves as a barrier to early dissemination. NR2F1 expression was decreased in patient ductal carcinoma in situ (DCIS) samples. High-resolution intravital imaging of HER2+ early-stage cancer cells revealed that loss of function of NR2F1 increased in vivo dissemination and was accompanied by decreased E-cadherin expression, activation of wingless-type MMTV integration site family, member 1 (WNT)-dependent β-catenin signaling, disorganized laminin 5 deposition, and increased expression of epithelial-mesenchymal transition (EMT) genes such as twist basic helix-loop-helix transcription factor 1 (TWIST1), zinc finger E-box binding homeobox 1 (ZEB1), and paired related homeobox 1 (PRRX1). Furthermore, downregulation of NR2F1 promoted a hybrid luminal/basal phenotype. NR2F1 expression was positively regulated by p38α signaling and repressed by HER2 and WNT4 pathways. Finally, early cancer cells with NR2F1LOW/PRRX1HIGH staining were observed in DCIS samples. Together, these findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 in early-stage breast cancer cells. SIGNIFICANCE: During early stages of breast cancer progression, HER2-mediated suppression of NR2F1 promotes dissemination by inducing EMT and a hybrid luminal/basal-like program.
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