ArticlePloS one2014
Microenvironmental stiffness enhances glioma cell proliferation by stimulating epidermal growth factor receptor signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 137 citations in OpenAlex.
- A mechanosensitive gene signature associated with immune landscape and survival in glioma: a multi-cohort analysis.Neurological research and practice · 2026Article
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- Discoidin domain receptor 1 (DDR1): An emerged novel mechanosensor.Fundamental research · 2026Review
- The Size of Glioblastoma Spheroids Influences Patterns of Invasion and Temozolomide Efficacy.Tissue engineering. Part C, Methods · 2026Article
- Hydrogel Microdroplet Based Glioblastoma Drug Screening Platform.Journal of biomedical materials research. Part A · 2026Article
- The Extracellular Matrix, the Silent 'Architect' of Glioma.Biomedicines · 2026Review
- Mechanical observables of cancer invasion: actin, adhesion, and metastatic plasticity.Frontiers in cell and developmental biology · 2026Review
- Mechanotransduction in glioma stem cell fate determination: from niche mechanics to therapeutic vulnerability and state plasticity.Frontiers in cell and developmental biology · 2026Review
- Construction of a 3D Bioprinted Microfluidic Platform to Study Breast Cancer Bone Metastasis and Tumor Microenvironmental Influences.ACS applied materials & interfaces · 2025Article
- The glioblastoma biomechanical landscape: A systematic review of magnetic resonance elastography (MRE) of brain tumors and healthy brain.APL bioengineering · 2025Review
- Size-dependent invasion and therapeutic phenotype of 42MGBA glioblastoma spheroids.bioRxiv : the preprint server for biology · 2025Article
- Hydrogel microdroplet based glioblastoma drug screening platform.bioRxiv : the preprint server for biology · 2025Article
- An Agrin-YAP/TAZ Rigidity Sensing Module Drives EGFR-Addicted Lung Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Radiation Damage to a Three-Dimensional Hydrogel Model of the Brain Perivascular Niche.Tissue engineering. Part C, Methods · 2025Article
- Profiling Glioma Stem Cell Dynamics via 3D-Based Cell Cycle Reporter Assays.Methods in molecular biology (Clifton, N.J.) · 2025Article
- An actin bracket-induced elastoplastic transition determines epithelial folding irreversibility.Nature communications · 2024Article
- The unfolded protein response sensor PERK mediates mechanical stress-induced maturation of focal adhesion complexes in glioblastoma cells.FEBS letters · 2024Article
- Discovery of miRNA-mRNA regulatory networks in glioblastoma reveals novel insights into tumor microenvironment remodeling.Scientific reports · 2024Article
- Glioma actively orchestrate a self-advantageous extracellular matrix to promote recurrence and progression.BMC cancer · 2024Review
- Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy.Cell reports. Medicine · 2024Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The aggressive and rapidly lethal brain tumor glioblastoma (GBM) is associated with profound tissue stiffening and genomic lesions in key members of the epidermal growth factor receptor (EGFR) pathway. Previous studies from our laboratory have shown that increasing microenvironmental stiffness in culture can strongly enhance glioma cell behaviors relevant to tumor progression, including proliferation, yet it has remained unclear whether stiffness and EGFR regulate proliferation through common or independent signaling mechanisms. Here we test the hypothesis that microenvironmental stiffness regulates cell cycle progression and proliferation in GBM tumor cells by altering EGFR-dependent signaling. We began by performing an unbiased reverse phase protein array screen, which revealed that stiffness modulates expression and phosphorylation of a broad range of signals relevant to proliferation, including members of the EGFR pathway. We subsequently found that culturing human GBM tumor cells on progressively stiffer culture substrates both dramatically increases proliferation and facilitates passage through the G1/S checkpoint of the cell cycle, consistent with an EGFR-dependent process. Western Blots showed that increasing microenvironmental stiffness enhances the expression and phosphorylation of EGFR and its downstream effector Akt. Pharmacological loss-of-function studies revealed that the stiffness-sensitivity of proliferation is strongly blunted by inhibition of EGFR, Akt, or PI3 kinase. Finally, we observed that stiffness strongly regulates EGFR clustering, with phosphorylated EGFR condensing into vinculin-positive focal adhesions on stiff substrates and dispersing as microenvironmental stiffness falls to physiological levels. Our findings collectively support a model in which tissue stiffening promotes GBM proliferation by spatially and biochemically amplifying EGFR signaling.
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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.