ArticleNature2004
Mechanotransduction through growth-factor shedding into the extracellular space.
Article in Nature, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 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
147 citing papers in PubMed, 357 citations in OpenAlex.
- Proliferation and differentiation in intestinal organoids are balanced by ligand-modulated EGFR trafficking.Life science alliance · 2026Article
- Mechanical force-induced tissue remodelling in a clinically relevant microphysiological model of asthmatic human lungs.Nature biomedical engineering · 2026Article
- Targeted shedding of extracellular membrane proteins by induced protease recruitment.bioRxiv : the preprint server for biology · 2026Article
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Just a little prick: careful cell contacts enabled by ceramic nanostraws.Pflugers Archiv : European journal of physiology · 2026Article
- De Novo Gene Transcription of Connexin Mediates Cytoplasmic Fluid Exchange and Flocking Transitions in Physiological and Cancerous Epithelial Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hic-5 drives epithelial mechanotransduction promoting a feed-forward cycle of bronchoconstriction.Nature communications · 2025Article
- MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation.Clinical and molecular hepatology · 2025Article
- Microdevice for confinement of T-cells on functionalized bio-interfaces.Lab on a chip · 2025Article
- Risk factors and management of lung cancer in idiopathic pulmonary fibrosis: A comprehensive review.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2025Article
- Forcing the code: tension modulates signaling to drive morphogenesis and malignancy.Genes & development · 2025Review
- An actin bracket-induced elastoplastic transition determines epithelial folding irreversibility.Nature communications · 2024Article
- A map of signaling responses in the human airway epithelium.Cell systems · 2024Article
- Modelling and targeting mechanical forces in organ fibrosis.Nature reviews bioengineering · 2024Article
- A gel-coated air-liquid-interface culture system with tunable substrate stiffness matching healthy and diseased lung tissues.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Integrating mechanical cues with engineered platforms to explore cardiopulmonary development and disease.iScience · 2023Review
- A life off the beaten track in biomechanics: Imperfect elasticity, cytoskeletal glassiness, and epithelial unjamming.Biophysics reviews · 2023Review
- Emerging roles and mechanisms of ERK pathway mechanosensing.Cellular and molecular life sciences : CMLS · 2023Review
- Innovative three-dimensional models for understanding mechanisms underlying lung diseases: powerful tools for translational research.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Piezo1 activates noncanonical EGFR endocytosis and signaling.Science advances · 2023Article
87 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
12 authors at 3 institutions in 1 country.
Funding
Abstract
Physical forces elicit biochemical signalling in a diverse array of cells, tissues and organisms, helping to govern fundamental biological processes. Several hypotheses have been advanced that link physical forces to intracellular signalling pathways, but in many cases the molecular mechanisms of mechanotransduction remain elusive. Here we find that compressive stress shrinks the lateral intercellular space surrounding epithelial cells, and triggers cellular signalling via autocrine binding of epidermal growth factor family ligands to the epidermal growth factor receptor. Mathematical analysis predicts that constant rate shedding of autocrine ligands into a collapsing lateral intercellular space leads to increased local ligand concentrations that are sufficient to account for the observed receptor signalling; direct experimental comparison of signalling stimulated by compressive stress versus exogenous soluble ligand supports this prediction. These findings establish a mechanism by which mechanotransduction arises from an autocrine ligand-receptor circuit operating in a dynamically regulated extracellular volume, not requiring induction of force-dependent biochemical processes within the cell or cell membrane.
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.