ArticleOncogene2020
TGFβ and EGF signaling orchestrates the AP-1- and p63 transcriptional regulation of breast cancer invasiveness.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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.
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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
58 citing papers in PubMed, 92 citations in OpenAlex.
- Fluctuating environment causes neoplastic transition and epithelial-mesenchymal plasticity in human cells.Research square · 2026Article
- The Role of AP-1 in Cancer: Regulation, Tumor Microenvironment and Therapeutic Targeting.Biomolecules · 2026Review
- 2-Hydroxyestradiol regulates extracellular matrix deposition through estrogen receptor beta activation in airway smooth muscle cells.Molecular and cellular endocrinology · 2026Article
- AP-1-Targeting Decoy Oligonucleotides: Mechanisms and Therapeutic Potential as Modulators of Inflammatory Pathways.Journal of cellular and molecular medicine · 2026Review
- Spatial Chromatin Accessibility Analysis of Intratumor Heterogeneity in Breast Cancer.Genomics, proteomics & bioinformatics · 2026Article
- Article
- Reciprocity between p63 and p21 via TNFα/NF-κB signaling in p63-positive salivary duct adenocarcinoma cell.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Extracellular Matrix-Related Prognostic Signature for Head and Neck Squamous Cell Carcinoma via Multi-Algorithm Survival Modeling.Biomarker insights · 2026Article
- Microenvironmental signals combine to induce non-additive molecular and phenotypic responses in mammary epithelial cells.iScience · 2025Article
- Mechanisms of breast cancer metastasis: the role of extracellular matrix.Molecular and cellular biochemistry · 2025Review
- Integrated spatial multi-omics profiling of Fusobacterium nucleatum in breast cancer unveils its role in tumour microenvironment modulation and cancer progression.Clinical and translational medicine · 2025Article
- Excessive MYC Orchestrates Macrophages induced Chromatin Remodeling to Sustain Micropapillary-Patterned Malignancy in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- TGF-β induces cholesterol accumulation to regulate the secretion of tumor-derived extracellular vesicles.Journal of experimental & clinical cancer research : CR · 2025Article
- IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth.Gut · 2025Article
- The transcription factor FOXQ1 in cancer.Cancer metastasis reviews · 2025Review
- CCL18 and EGF May Serve as Potential Prognostic Biomarkers and Therapeutic Targets for Human Breast Cancer.International journal of breast cancer · 2025Article
- Inflammation-associated drug resistance and tumor growth in TNBC.Frontiers in immunology · 2025Review
- Exploring TGF-β Signaling in Cancer Progression: Prospects and Therapeutic Strategies.OncoTargets and therapy · 2025Review
- Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity.Nucleic acids research · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activator protein (AP)-1 transcription factors are essential elements of the pro-oncogenic functions of transforming growth factor-β (TGFβ)-SMAD signaling. Here we show that in multiple HER2+ and/or EGFR+ breast cancer cell lines these AP-1-dependent tumorigenic properties of TGFβ critically rely on epidermal growth factor receptor (EGFR) activation and expression of the ΔN isoform of transcriptional regulator p63. EGFR and ΔNp63 enabled and/or potentiated the activation of a subset of TGFβ-inducible invasion/migration-associated genes, e.g., ITGA2, LAMB3, and WNT7A/B, and enhanced the recruitment of SMAD2/3 to these genes. The TGFβ- and EGF-induced binding of SMAD2/3 and JUNB to these gene loci was accompanied by p63-SMAD2/3 and p63-JUNB complex formation. p63 and EGFR were also found to strongly potentiate TGFβ induction of AP-1 proteins and, in particular, FOS family members. Ectopic overexpression of FOS could counteract the decrease in TGFβ-induced gene activation after p63 depletion. p63 is also involved in the transcriptional regulation of heparin binding (HB)-EGF and EGFR genes, thereby establishing a self-amplification loop that facilitates and empowers the pro-invasive functions of TGFβ. These cooperative pro-oncogenic functions of EGFR, AP-1, p63, and TGFβ were efficiently inhibited by clinically relevant chemical inhibitors. Our findings may, therefore, be of importance for therapy of patients with breast cancers with an activated EGFR-RAS-RAF pathway.
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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.