ArticleFrontiers in cell and developmental biology2023
Extracellular matrix stiffness activates mechanosensitive signals but limits breast cancer cell spheroid proliferation and invasion.
Article in Frontiers in cell and developmental biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Current Perspectives on 2D and 3D Cell Culture Models in Cancer Research: Molecular Determinants of Tumor Biology and Therapeutic Response.Current issues in molecular biology · 2026Review
- Engineering Biomimetic 3D Microenvironments for Extracellular Vesicle Programming Toward Clinical Translation.International journal of molecular sciences · 2026Review
- Mechanobiology of the tumor microenvironment: a review of therapeutic interactions and in vitro elasticity measurement techniques.Journal of biomedical science · 2026Review
- Decoupling Mechanical Confinement and Fibrotic Extracellular Matrix Signaling in Vestibular Schwannoma Using Tunable 3D Hydrogels.Cellular and molecular bioengineering · 2026Article
- Establishing the first Afro-Caribbean breast cancer cell lines reveals ECM pathway enrichment and distinctive drug sensitivities.Scientific reports · 2026Article
- Amoeboid-mesenchymal transition and the proteolytic control of cancer invasion plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tumor microenvironment and key signaling pathways in breast cancer progression and therapy resistance: A review.Biomolecules & biomedicine · 2026Review
- Hydroxyapatite-Mediated Mechanical Modulation of GelMA Hydrogels Influences Osteogenic Differentiation of 3D Spheroids.Gels (Basel, Switzerland) · 2026Article
- An animal component-free bioprocess for synthesizing 3D human matrix scaffolds using mesenchymal stromal cells.Frontiers in cell and developmental biology · 2026Article
- Is there a link between fascia and cancer? From potential mechanisms to future treatment options.Frontiers in physiology · 2026Review
- Cancer-associated fibroblasts at the crossroads of tumor progression and therapy resistance: from heterogeneity to precision reprogramming.Journal of the Egyptian National Cancer Institute · 2025Review
- Dissecting the Non-Immune Tumor Microenvironment in Triple-Negative Breast Cancer: Molecular Subtype-Specific Patterns and Prognostic Implications.International journal of molecular sciences · 2025Review
- Three-dimensional spheroid models for cardiovascular biology and pathology.Mechanobiology in medicine · 2025Review
- Multimodal Phasor Approach to Study Breast Cancer Cell Invasion in a 3D Spheroid Model.Chemical & biomedical imaging · 2025Article
- Gravitational forces and matrix stiffness modulate the invasiveness of breast cancer cells in bioprinted spheroids.Materials today. Bio · 2025Article
- Review
- Quantitative characterization of the 3D self-organization of PDAC tumor spheroids reveals cell type and matrix dependence through advanced microscopy analysis.APL bioengineering · 2025Article
- Reprogramming the tumor microenvironment to boost adoptive T cell therapy.Frontiers in immunology · 2025Review
- A hybrid computational model of cancer spheroid growth with ribose-induced collagen stiffening.Frontiers in bioengineering and biotechnology · 2025Article
- Defining and modeling dynamic spatial heterogeneity within tumor microenvironments.Current opinion in cell biology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is characterized by physical changes that occur in the tumor microenvironment throughout growth and metastasis of tumors. Extracellular matrix stiffness increases as tumors develop and spread, with stiffer environments thought to correlate with poorer disease prognosis. Changes in extracellular stiffness and other physical characteristics are sensed by integrins which integrate these extracellular cues to intracellular signaling, resulting in modulation of proliferation and invasion. However, the co-ordination of mechano-sensitive signaling with functional changes to groups of tumor cells within 3-dimensional environments remains poorly understood. Here we provide evidence that increasing the stiffness of collagen scaffolds results in increased activation of ERK1/2 and YAP in human breast cancer cell spheroids. We also show that ERK1/2 acts upstream of YAP activation in this context. We further demonstrate that YAP, matrix metalloproteinases and actomyosin contractility are required for collagen remodeling, proliferation and invasion in lower stiffness scaffolds. However, the increased activation of these proteins in higher stiffness 3-dimensional collagen gels is correlated with reduced proliferation and reduced invasion of cancer cell spheroids. Our data collectively provide evidence that higher stiffness 3-dimensional environments induce mechano-signaling but contrary to evidence from 2-dimensional studies, this is not sufficient to promote pro-tumorigenic effects in breast cancer cell spheroids.
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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.