ArticleThe Journal of clinical investigation2014
Multifactorial ERβ and NOTCH1 control of squamous differentiation and cancer.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 61 citations in OpenAlex.
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- Identification of PI3K/AKT/mTOR-related genes as diagnostic biomarkers for cutaneous squamous cell carcinoma.Biochemistry and biophysics reports · 2026Article
- Tongue cancer in pregnancy: challenges and outcomes. A case series and review of the literature.Oral and maxillofacial surgery · 2025Review
- Sex Bias in Autoimmunity: New Findings and New Opportunities.JID innovations : skin science from molecules to population health · 2025Review
- 101 Machine Learning Algorithms for Mining Esophageal Squamous Cell Carcinoma Neoantigen Prognostic Models in Single-Cell Data.International journal of molecular sciences · 2025Article
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- Sex as a Biological Variable in Early-Phase Oncology Clinical Trials: Enhancing the Path to Personalised Medicine.Heliyon · 2024Review
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- The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome.Nature communications · 2023Article
- PRDM16 from hepatic stellate cells-derived extracellular vesicles promotes hepatocellular carcinoma progression.American journal of cancer research · 2023Article
- Article
- Exploring Potential Biomarkers, Ferroptosis Mechanisms, and Therapeutic Targets Associated with Cutaneous Squamous Cell Carcinoma via Integrated Transcriptomic Analysis.Journal of healthcare engineering · 2022Article
- Activation of bivalent factor DLX5 cooperates with master regulator TP63 to promote squamous cell carcinoma.Nucleic acids research · 2021Article
- Article
- Cystatin-B Negatively Regulates the Malignant Characteristics of Oral Squamous Cell Carcinoma PossiblyFrontiers in oncology · 2021Article
- DLX5 promotes osteosarcoma progression via activation of the NOTCH signaling pathway.American journal of cancer research · 2021Article
- Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer.Molecular & cellular proteomics : MCP · 2020Article
- CSL controls telomere maintenance and genome stability in human dermal fibroblasts.Nature communications · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 8 institutions in 3 countries.
Funding
Abstract
Downmodulation or loss-of-function mutations of the gene encoding NOTCH1 are associated with dysfunctional squamous cell differentiation and development of squamous cell carcinoma (SCC) in skin and internal organs. While NOTCH1 receptor activation has been well characterized, little is known about how NOTCH1 gene transcription is regulated. Using bioinformatics and functional screening approaches, we identified several regulators of the NOTCH1 gene in keratinocytes, with the transcription factors DLX5 and EGR3 and estrogen receptor β (ERβ) directly controlling its expression in differentiation. DLX5 and ERG3 are required for RNA polymerase II (PolII) recruitment to the NOTCH1 locus, while ERβ controls NOTCH1 transcription through RNA PolII pause release. Expression of several identified NOTCH1 regulators, including ERβ, is frequently compromised in skin, head and neck, and lung SCCs and SCC-derived cell lines. Furthermore, a keratinocyte ERβ-dependent program of gene expression is subverted in SCCs from various body sites, and there are consistent differences in mutation and gene-expression signatures of head and neck and lung SCCs in female versus male patients. Experimentally increased ERβ expression or treatment with ERβ agonists inhibited proliferation of SCC cells and promoted NOTCH1 expression and squamous differentiation both in vitro and in mouse xenotransplants. Our data identify a link between transcriptional control of NOTCH1 expression and the estrogen response in keratinocytes, with implications for differentiation therapy of squamous cancer.
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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.