ArticleThe Journal of clinical investigation2007
Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 370 papers, 2 of them syntheses that pooled it.
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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
370 citing papers in PubMed, 2 syntheses or guidelines pooled it, 659 citations in OpenAlex.
- A Comprehensive Meta-Analysis of Association between EGFR Mutation Status and Brain Metastases in NSCLC.Pathology oncology research : POR · 2019Pooled it
- Pooled it
- A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer.Cancer chemotherapy and pharmacology · 2022Trial
- A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2017Trial
- STAT3 signaling mediates EGFR-TKI resistance in non-small cell lung cancer by regulating stemness markers and telomerase, reversed by icaritin.British journal of cancer · 2026Article
- Exploring the mechanism of action of glaucocalyxin D against acute myeloid leukemia using network pharmacology, molecular docking and cellular experiments.Oncology letters · 2026Article
- Review
- Clinical Outcomes and Safety of Concurrent Chemoradiotherapy inJTO clinical and research reports · 2026Article
- Circadian Rhythms in Cancer: Mechanistic Insights, Chronotherapeutic Strategies, and Translational Challenges.Annals of surgical oncology · 2026Review
- The STAT3-ZEB1 axis contributes to CCL2-mediated resistance to osimertinib in lung cancer.Frontiers in oncology · 2026Article
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- The Potential of Nutraceutical Supplementation in Counteracting Cancer Development and Progression: A Pathophysiological Perspective.Nutrients · 2025Review
- The Diverse Function of IL-6 in Biological Processes and the Advancement of Cancer.Immune network · 2025Review
- Prognostic and predictive values of a multimodal nomogram incorporating tumor and peritumor morphology with immune status in resectable lung adenocarcinoma.Journal for immunotherapy of cancer · 2025Article
- Machine learning identifies clinical tumor mutation landscape pathways of resistance to checkpoint inhibitor therapy in NSCLC.Journal for immunotherapy of cancer · 2025Article
- Overexpression of IL-6 and STAT3 may provide new insights into ovine pulmonary adenocarcinoma development.BMC veterinary research · 2025Article
- The anticancer activity and mechanisms of She medicine herbs.Frontiers in pharmacology · 2025Review
- Novel immunotherapy combinations in neoadjuvant non-small cell lung cancer (NSCLC): a better chance at cure?Translational lung cancer research · 2024Article
- Chemerin promotes invasion of oral squamous cell carcinoma by stimulating IL-6 and TNF-α production via STAT3 activation.Molecular biology reports · 2024Article
- Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.Current issues in molecular biology · 2024Review
310 more citing papers are in PubMed but not listed here.
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11 authors at 1 institution in 1 country.
Funding
Abstract
Persistently activated or tyrosine-phosphorylated STAT3 (pSTAT3) is found in 50% of lung adenocarcinomas. pSTAT3 is found in primary adenocarcinomas and cell lines harboring somatic-activating mutations in the tyrosine kinase domain of EGFR. Treatment of cell lines with either an EGFR inhibitor or an src kinase inhibitor had no effect on pSTAT3 levels, whereas a pan-JAK inhibitor (P6) blocked activation of STAT3 and inhibited tumorigenesis. Cell lines expressing these persistently activated mutant EGFRs also produced high IL-6 levels, and blockade of the IL-6/gp130/JAK pathway led to a decrease in pSTAT3 levels. In addition, reduction of IL-6 levels by RNA interference led to a decrease in tumorigenesis. Introduction of persistently activated EGFR into immortalized breast epithelial cells led to tumorigenesis, IL-6 expression, and STAT3 activation, all of which could be inhibited with P6 or gp130 blockade. Furthermore, inhibition of EGFR activity in multiple cell lines partially blocked transcription of IL-6 and concurrently decreased production and release of IL-6. Finally, immunohistochemical analysis revealed a positive correlation between pSTAT3 and IL-6 positivity in primary lung adenocarcinomas. Therefore, mutant EGFR could activate the gp130/JAK/STAT3 pathway by means of IL-6 upregulation in primary human lung adenocarcinomas, making this pathway a potential target for cancer treatment.
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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.