ArticleNature cell biology2021
Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling.
Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 90 papers, 1 of them a synthesis that pooled it.
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
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Proliferation and differentiation in intestinal organoids are balanced by ligand-modulated EGFR trafficking.Life science alliance · 2026Article
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- Lactate as a Master Regulator of Immune Suppression: From Metabolic Waste to Epigenetic Checkpoint in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Comprehensive overview of AI methodologies in nano-drug delivery Optimization and Design.NPJ precision oncology · 2026Review
- Gastric Cancer Organoids: Mechanistic Insights, Drug Discovery, and Translational Advances in Precision Medicine.Journal of gastric cancer · 2026Review
- A Constellation of Fluorescent Biosensors to Illuminate the Galaxy of Protein Kinases.Chembiochem : a European journal of chemical biology · 2026Review
- Integrative Proteogenomic Characterization of Left-Sided and Right-Sided Colorectal Cancer.MedComm · 2026Article
- Dynamic visualization of physiological CaMKII activity using sensitive FRET biosensors.bioRxiv : the preprint server for biology · 2026Article
- Preservation of Human Colonic Stem Cells Requires an ERK Dynamics Checkpoint Mediated by AKT.bioRxiv : the preprint server for biology · 2026Article
- Functional Exploration of African Colorectal Cancer Patients Using PersonalisedbioRxiv : the preprint server for biology · 2026Article
- Multidimensional data analysis and classification using SMIAL.Communications biology · 2026Article
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Article
- Hepatocellular carcinoma-linkediScience · 2026Article
- Exploratory biomarker analysis of RAS/BRAF somatic mutations and gene expression signatures for predicting treatment effects of aflibercept in the velour trial.NPJ precision oncology · 2026Article
- CNAScope: pan-cancer copy number aberration database with functional annotation and interactive visualization.Nucleic acids research · 2026Article
- Patient-derived organoids (PDOs) as a promising platform for personalized treatment of colorectal cancer: current applications and future challenges.Cancer biology & therapy · 2025Review
- Non-canonical EGFR signaling promotes MAPK-dependent extrusion of epithelial cells.Journal of cell science · 2025Article
- Two novel red-FRET ERK bosensors in the 670-720 nm range.Journal of biological engineering · 2025Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
Abstract
Direct targeting of the downstream mitogen-activated protein kinase (MAPK) pathway to suppress extracellular-regulated kinase (ERK) activation in KRAS and BRAF mutant colorectal cancer (CRC) has proven clinically unsuccessful, but promising results have been obtained with combination therapies including epidermal growth factor receptor (EGFR) inhibition. To elucidate the interplay between EGF signalling and ERK activation in tumours, we used patient-derived organoids (PDOs) from KRAS and BRAF mutant CRCs. PDOs resemble in vivo tumours, model treatment response and are compatible with live-cell microscopy. We established real-time, quantitative drug response assessment in PDOs with single-cell resolution, using our improved fluorescence resonance energy transfer (FRET)-based ERK biosensor EKAREN5. We show that oncogene-driven signalling is strikingly limited without EGFR activity and insufficient to sustain full proliferative potential. In PDOs and in vivo, upstream EGFR activity rigorously amplifies signal transduction efficiency in KRAS or BRAF mutant MAPK pathways. Our data provide a mechanistic understanding of the effectivity of EGFR inhibitors within combination therapies against KRAS and BRAF mutant CRC.
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.