ArticleMatrix biology : journal of the International Society for Matrix Biology2020
Scaffold stiffness influences breast cancer cell invasion via EGFR-linked Mena upregulation and matrix remodeling.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- 3DACS biomaterials science & engineering · 2023Pooled it
- Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion.Cell biomaterials · 2026Article
- Discoidin domain receptor 1 (DDR1): An emerged novel mechanosensor.Fundamental research · 2026Review
- 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
- Mineralized Cryogel/Hydrogel Constructs to Recapitulate Early Breast Cancer Bone Metastasis In Vitro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Gelatin-methacryloyl hydrogel stiffness influences epithelial-mesenchymal transition in MCF7 but not MDA-MB-231 breast cancer cells in 3D culture.Biology open · 2026Article
- Fibronectin Is a Likely Therapeutic Target Shared by Oral and Breast Carcinomas.International journal of molecular sciences · 2026Article
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- Integrin-Piezo1 Axis Drives ECM Remodeling and Invasion of 3D Breast Epithelium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Semaphorin-7A promotes macrophage-mediated mammary epithelial and ductal carcinoma in situ invasion.Breast cancer research : BCR · 2025Article
- Propofol suppresses breast cancer invasion: An in vitro three-dimensional cell invasion model with microfluidic technology.Journal of applied biomedicine · 2025Article
- Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion.bioRxiv : the preprint server for biology · 2025Article
- Review
- Three-dimensional spheroid models for cardiovascular biology and pathology.Mechanobiology in medicine · 2025Review
- Collagen fiber density observed in metastatic ovarian cancer promotes tumor cell adhesion.Acta biomaterialia · 2025Article
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- FN1 shapes the behavior of papillary thyroid carcinoma through alternative splicing of EDB region.Scientific reports · 2025Article
- A hybrid computational model of cancer spheroid growth with ribose-induced collagen stiffening.Frontiers in bioengineering and biotechnology · 2025Article
- Matrix stiffness regulates NPC invasiveness by modulating a mechanoresponsive TRPV4-Nox4-IL-8 signaling axis.Journal of Cancer · 2025Article
- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Clinically, increased breast tumor stiffness is associated with metastasis and poorer outcomes. Yet, in vitro studies of tumor cells in 3D scaffolds have found decreased invasion in stiffer environments. To resolve this apparent contradiction, MDA-MB-231 breast tumor spheroids were embedded in 'low' (2 kPa) and 'high' (12 kPa) stiffness 3D hydrogels comprised of methacrylated gelatin/collagen I, a material that allows for physiologically-relevant changes in stiffness while matrix density is held constant. Cells in high stiffness materials exhibited delayed invasion, but more abundant actin-enriched protrusions, compared to those in low stiffness. We find that cells in high stiffness had increased expression of Mena, an invadopodia protein associated with metastasis in breast cancer, as a result of EGFR and PLCγ1 activation. As invadopodia promote invasion through matrix remodeling, we examined matrix organization and determined that spheroids in high stiffness displayed a large fibronectin halo. Interestingly, this halo did not result from increased fibronectin production, but rather from Mena/α5 integrin dependent organization. In high stiffness environments, FN1 knockout inhibited invasion while addition of exogenous cellular fibronectin lessened the invasion delay. Analysis of fibronectin isoforms demonstrated that EDA-fibronectin promoted invasion and that clinical invasive breast cancer specimens displayed elevated EDA-fibronectin. Combined, our data support a mechanism by which breast cancer cells respond to stiffness and render the environment conducive to invasion. More broadly, these findings provide important insight on the roles of matrix stiffness, composition, and organization in promoting tumor invasion.
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