ArticleMolecular biology of the cell2015
Enhanced dimerization drives ligand-independent activity of mutant epidermal growth factor receptor in lung cancer.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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
61 citing papers in PubMed, 98 citations in OpenAlex.
- IgE Occupancy and Antigen Valency Cooperate to Control FcεRI Aggregation Geometry and Signaling Efficiency.International journal of molecular sciences · 2026Article
- VEGFR2 dimerization kinetics on the cell surface determined by microscopy and mathematical modeling.Biophysical journal · 2026Article
- Graph neural network modeling of receptor interaction kinetics from single-molecule imaging data.bioRxiv : the preprint server for biology · 2026Article
- Integrative structural and dynamics studies of epidermal growth factor receptor (EGFR).Experimental & molecular medicine · 2026Review
- Tetraspanin CD82 shapes EGFR signaling outcomes through nanoscale receptor organization.The Journal of cell biology · 2026Article
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Single-Molecule FRET-Tracking of InlB-Activated MET Receptors in Living Cells.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Steric disruption of EGFR oligomerization overcomes therapy resistance in non-small cell lung cancer.Science advances · 2025Article
- Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods.Biophysical journal · 2025Review
- IgE occupancy and antigen valency cooperate to control FcεRI aggregation geometry and signaling efficiency.bioRxiv : the preprint server for biology · 2025Article
- An Orally Available Grafted Peptide Targeting Epidermal Growth Factor Receptor Dimers Reduces Non-Small Cell Lung Cancer Tumors in Mouse Models.ACS pharmacology & translational science · 2025Article
- Antigen properties shape organization of FcεRI aggregates to tune mast cell signaling.bioRxiv : the preprint server for biology · 2025Article
- Quantitative evaluation of methods to analyze motion changes in single-particle experiments.Nature communications · 2025Article
- Imaging Ligand-Receptor Interactions at Single-Protein Resolution with DNA-PAINT.Small methods · 2025Article
- Single-molecule localization microscopy as a tool to quantify di/oligomerization of receptor tyrosine kinases and G protein-coupled receptors.Molecular pharmacology · 2025Review
- Clinical outcome analysis of different first‑ and second‑generation EGFR‑tyrosine kinase inhibitors in untreated patients with EGFR‑mutated non‑small cell lung cancer with baseline brain metastasis.Oncology letters · 2025Article
- Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes.Cell reports · 2024Article
- Tolerance to aberration and misalignment in a two-point-resolving image inversion interferometer.Optics express · 2023Article
- High-precision estimation of emitter positions using Bayesian grouping of localizations.Nature communications · 2022Article
- Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
1 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
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations within the epidermal growth factor receptor (EGFR/erbB1/Her1) are often associated with tumorigenesis. In particular, a number of EGFR mutants that demonstrate ligand-independent signaling are common in non-small cell lung cancer (NSCLC), including kinase domain mutations L858R (also called L834R) and exon 19 deletions (e.g., ΔL747-P753insS), which collectively make up nearly 90% of mutations in NSCLC. The molecular mechanisms by which these mutations confer constitutive activity remain unresolved. Using multiple subdiffraction-limit imaging modalities, we reveal the altered receptor structure and interaction kinetics of NSCLC-associated EGFR mutants. We applied two-color single quantum dot tracking to quantify receptor dimerization kinetics on living cells and show that, in contrast to wild-type EGFR, mutants are capable of forming stable, ligand-independent dimers. Two-color superresolution localization microscopy confirmed ligand-independent aggregation of EGFR mutants. Live-cell Förster resonance energy transfer measurements revealed that the L858R kinase mutation alters ectodomain structure such that unliganded mutant EGFR adopts an extended, dimerization-competent conformation. Finally, mutation of the putative dimerization arm confirmed a critical role for ectodomain engagement in ligand-independent signaling. These data support a model in which dysregulated activity of NSCLC-associated kinase mutants is driven by coordinated interactions involving both the kinase and extracellular domains that lead to enhanced dimerization.
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.