ArticleMolecular carcinogenesis2013
STAT1 gene expression is enhanced by nuclear EGFR and HER2 via cooperation with STAT3.
Article in Molecular carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
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- A Non-Canonical p75HER2 Signaling Pathway Underlying Trastuzumab Action and Resistance in Breast Cancer.Cells · 2024Article
- Inherited human ZNF341 deficiency.Current opinion in immunology · 2023Review
- Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities.Nature communications · 2023Article
- Lapatinib dysregulates HER2 signaling and impairs the viability of human uveal melanoma cells.Journal of Cancer · 2023Article
- Nuclear export signal mutation of epidermal growth factor receptor enhances malignant phenotypes of cancer cells.American journal of cancer research · 2023Article
- STAT family of transcription factors in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Seminars in cancer biology · 2022Review
- Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The multi-kinase inhibitor afatinib serves as a novel candidate for the treatment of human uveal melanoma.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Inclusion Body Myositis and Neoplasia: A Narrative Review.International journal of molecular sciences · 2022Review
- Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy.Molecular therapy oncolytics · 2022Article
- Cold atmospheric plasma for preventing infection of viruses that use ACE2 for entry.Theranostics · 2022Article
- Primaquine Inhibits the Endosomal Trafficking and Nuclear Localization of EGFR and Induces the Apoptosis of Breast Cancer Cells by Nuclear EGFR/Stat3-Mediated c-Myc Downregulation.International journal of molecular sciences · 2021Article
- Article
- Human RNase3 immune modulation by catalytic-dependent and independent modes in a macrophage-cell line infection model.Cellular and molecular life sciences : CMLS · 2021Article
- Nuclear ErbB2 expression in hepatocytes in liver disease.Virchows Archiv : an international journal of pathology · 2021Article
- STAT1 expression and HPV16 viral load predict cervical lesion progression.Oncology letters · 2020Article
- Hedgehog Signaling and Truncated GLI1 in Cancer.Cells · 2020Review
- Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models.Cancers · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Both EGFR and HER2 are important mediators of tumorigenesis and tumor progression. Despite their best-characterized roles as plasma membrane-bound receptors, both receptors undergo nuclear translocation though the impact of this process remains unclear. In this study, we provide evidence showing that EGFR upregulates expression of signal transducer and activator of transcription 1 (STAT1), a transcription factor responding to inflammatory signals and regulating genes involved in inflammatory response. EGFR regulation of STAT1 expression is primarily attributed to the nuclear activity of EGFR. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression. Structural characterization of the human STAT1 gene promoter indicates the presence of four functional STAT3-binding sites in the promoter and their importance in STAT1 co-regulation by EGFR and STAT3. The constitutively activated EGFR variant, EGFRvIII, also cooperates with STAT3 to activate the STAT1 gene promoter through the identified STAT3-binding sites within the promoter. Using human breast cancer cell lines, we further found a positive association between levels of STAT1, EGFR, and p-STAT3. Furthermore, we found that STAT1 expression is transcriptionally upregulated by HER2 and heregulin stimulation in breast cancer cells, and the level is further augmented by activated STAT3. In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1.
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Registered trials
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