ArticleNature communications2014
Constitutive and ligand-induced EGFR signalling triggers distinct and mutually exclusive downstream signalling networks.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
64 citing papers in PubMed, 94 citations in OpenAlex.
- Ligand-activated EGFR/MAPK signaling but not PI3K, are key resistance mechanisms to EGFR-therapy in colorectal cancer.Nature communications · 2025Trial
- Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment.Cancers · 2026Review
- A Novel Tyrosine Kinase Axis in Innate Immune Signaling.Viruses · 2025Review
- High precision fluorescence tomography system for pre-clinical radiation research: system design and validation.Physics in medicine and biology · 2025Article
- EGFR-STAT1 pathway drives fibrosis initiation in fibroinflammatory skin diseases.Nature communications · 2025Article
- LncRNA EUDAL shapes tumor cell response to hypoxia-induced constitutive EGFR activation and promotes chemoresistance in oral cancer.International journal of oral science · 2025Article
- Oncogenic RARγ isoforms promote head and neck cancer proliferation through vinexin-β-mediated cell cycle acceleration and autocrine activation of EGFR signal.International journal of biological sciences · 2025Article
- SPP1 expression indicates outcome of immunotherapy plus tyrosine kinase inhibition in advanced renal cell carcinoma.Human vaccines & immunotherapeutics · 2024Article
- A novel role for WZ3146 in the inhibition of cell proliferation via ERK and AKT pathway in the rare EGFR G719X mutant cells.Scientific reports · 2024Article
- Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers.Nature communications · 2024Article
- CytoCopasi: a chemical systems biology target and drug discovery visual data analytics platform.Bioinformatics (Oxford, England) · 2023Article
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- EGFR promotes the apoptosis of CD4Journal of advanced research · 2023Article
- BMX controls 3βHSD1 and sex steroid biosynthesis in cancer.The Journal of clinical investigation · 2023Article
- Osteopontin and Cancer: Insights into Its Role in Drug Resistance.Biomedicines · 2023Review
- EGFR trafficking: effect of dimerization, dynamics, and mutation.Frontiers in oncology · 2023Review
- Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation.Nature communications · 2022Article
- A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations.Nature communications · 2022Article
- The PSI Domain of the MET Oncogene Encodes a Functional Disulfide Isomerase Essential for the Maturation of the Receptor Precursor.International journal of molecular sciences · 2022Article
- A Bioinformatics-Based Analysis of an Anoikis-Related Gene Signature Predicts the Prognosis of Patients with Low-Grade Gliomas.Brain sciences · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Epidermal growth factor receptor (EGFR) overexpression plays an important oncogenic role in cancer. Regular EGFR protein levels are increased in cancer cells and the receptor then becomes constitutively active. However, downstream signals generated by constitutively activated EGFR are unknown. Here we report that the overexpressed EGFR oscillates between two distinct and mutually exclusive modes of signalling. Constitutive or non-canonical EGFR signalling activates the transcription factor IRF3 leading to expression of IFI27, IFIT1 and TRAIL. Ligand-mediated activation of EGFR switches off IRF3-dependent transcription, activates canonical extracellular signal-regulated kinase (ERK) and Akt signals, and confers sensitivity to chemotherapy and virus-induced cell death. Mechanistically, the distinct downstream signals result from a switch of EGFR-associated proteins. EGFR constitutively complexes with IRF3 and TBK1 leading to TBK1 and IRF3 phosphorylation. Addition of epidermal growth factor dissociates TBK1, IRF3 and EGFR leading to a loss of IRF3 activity, Shc-EGFR association and ERK activation. Finally, we provide evidence for non-canonical EGFR signalling in glioblastoma.
Indexed as
Identifiers
What OpenQuestion holds
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.