ArticleNature communications2015
Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
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Who cites it
40 citing papers in PubMed, 80 citations in OpenAlex.
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- TM9SF4 acts as a receptor mediatingFrontiers in cellular and infection microbiology · 2026Article
- Acquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat.Neoplasia (New York, N.Y.) · 2025Article
- Cold atmospheric plasma potentiates ferroptosis via EGFR(Y1068)-mediated dual axes on GPX4 among triple negative breast cancer cells.International journal of biological sciences · 2025Article
- Targeting solid tumor antigens with chimeric receptors: cancer biology meets synthetic immunology.Trends in cancer · 2024Review
- Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer.Scientific reports · 2024Article
- Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes.Molecular biology of the cell · 2023Article
- Review
- EGF, TGF-International journal of molecular sciences · 2023Article
- Epidermal growth factor alters silica nanoparticle uptake and improves gold-nanoparticle-mediated gene silencing in A549 cells.Frontiers in nanotechnology · 2023Article
- Influence of EGF and pro-NGF on EGFR/SORTILIN interaction and clinical impact in head and neck squamous cell carcinoma.Frontiers in oncology · 2023Article
- Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF.International journal of nanomedicine · 2023Article
- Proteasomal deubiquitylase activity enhances cell surface recycling of the epidermal growth factor receptor in non-small cell lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- The effects of CD148 Q276P/R326Q polymorphisms in A431D epidermoid cancer cell proliferation and epidermal growth factor receptor signaling.Cancer reports (Hoboken, N.J.) · 2022Article
- Deciphering signal transduction networks in the liver by mechanistic mathematical modelling.The Biochemical journal · 2022Article
- A scalable, open-source implementation of a large-scale mechanistic model for single cell proliferation and death signaling.Nature communications · 2022Article
- Epidermal growth factor receptor (EGFR) expression in the serum of patients with triple-negative breast carcinoma: prognostic value of this biomarker.Ecancermedicalscience · 2022Article
- Improving the detection of aggressive prostate cancer using immunohistochemical staining of protein marker panels.American journal of cancer research · 2022Article
- G protein pathway suppressor 2 suppresses gastric cancer by destabilizing epidermal growth factor receptor.Cancer science · 2021Article
- QSPcc reduces bottlenecks in computational model simulations.Communications biology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Ubiquitination of the epidermal growth factor receptor (EGFR) that occurs when Cbl and Grb2 bind to three phosphotyrosine residues (pY1045, pY1068 and pY1086) on the receptor displays a sharp threshold effect as a function of EGF concentration. Here we use a simple modelling approach together with experiments to show that the establishment of the threshold requires both the multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR. While the threshold is remarkably robust, a more sophisticated model predicted that it could be modulated as a function of EGFR levels on the cell surface. We confirmed experimentally that the system has evolved to perform optimally at physiological levels of EGFR. As a consequence, this system displays an intrinsic weakness that causes--at the supraphysiological levels of receptor and/or ligand associated with cancer--uncoupling of the mechanisms leading to signalling through phosphorylation and attenuation through ubiquitination.
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.