ArticleBiophysical journal2020
Increased Stiffness Inhibits Invadopodia Formation and Cell Migration in 3D.
Article in Biophysical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Hallmarks of epithelial-mesenchymal plasticity in cancer.Molecular cancer · 2026Review
- Integrated transcriptome and proteome analyses unveil cytoskeletal alterations in an endothelial model of monogenic diabetes.Genome medicine · 2026Article
- Leveraging crosslinker diffusion to template stiffness gradients in alginate hydrogels.Biomedical materials (Bristol, England) · 2025Article
- Biomechanics of the tumor extracellular matrix and regulatory T cells: regulatory mechanisms and potential therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- Non-canonical ALK7 pathways promote pancreatic cancer metastasis through β-catenin/MMP-mediated basement membrane breakdown and intravasation.Molecular cancer · 2025Article
- Regulation of cell migration by extracellular matrix mechanics at a glance.Journal of cell science · 2025Review
- Hydrogel Design to Understand and Guide 3D Cell Migration.Regenerative engineering and translational medicine · 2025Review
- Mechanical signatures in cancer metastasis.npj biological physics and mechanics · 2025Review
- A hybrid computational model of cancer spheroid growth with ribose-induced collagen stiffening.Frontiers in bioengineering and biotechnology · 2025Article
- Differential stiffness between brain vasculature and parenchyma promotes metastatic infiltration through vessel co-option.Nature cell biology · 2024Article
- Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination.Cancer metastasis reviews · 2024Review
- Matrix stiffness-dependent regulation of immunomodulatory genes in human MSCs is associated with the lncRNA CYTOR.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cell volume expansion and local contractility drive collective invasion of the basement membrane in breast cancer.Nature materials · 2024Article
- Pathological and Therapeutic Significance of Tumor-Derived Extracellular Vesicles in Cancer Cell Migration and Metastasis.Cancers · 2023Review
- Precision Hydrogels for the Study of Cancer Cell Mechanobiology.Advanced healthcare materials · 2023Review
- Getting physical: Material mechanics is an intrinsic cell cue.Cell stem cell · 2023Review
- Article
- Dynamically Crosslinked Poly(ethylene-glycol) Hydrogels Reveal a Critical Role of Viscoelasticity in Modulating Glioblastoma Fates and Drug Responses in 3D.Advanced healthcare materials · 2023Article
- Unravelling cell migration: defining movement from the cell surface.Cell adhesion & migration · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer cells typically invade through basement membranes (BMs) at key points during metastasis, including primary tumor invasion, intravasation, and extravasation. Cells extend invadopodia protrusions to create channels in the nanoporous BM through which they can invade, either via proteolytic degradation or mechanical force. Increased matrix stiffness can promote cancer progression, and two-dimensional (2D) culture studies indicate that increased stiffness promotes invadopodia degradation activity. However, invadopodia can function mechanically, independent of their degradative activity, and cells do not form fully matured invadopodia or migrate in the direction of the invadopodia in 2D environments. Here, we elucidated the impact of matrix stiffness on the mechanical mode of invadopodia activity of cancer cells cultured in three-dimensional BM-like matrices. Invadopodia formation and cell migration assays were performed for invasive breast cancer cells cultured in mechanically plastic, nanoporous, and minimally degradable interpenetrating networks of reconstituted BM matrix and alginate, which presented a range of elastic moduli from 0.4 to 9.3 kPa. Across this entire range of stiffness, we find that cells form mature invadopodia that often precede migration in the direction of the protrusion. However, at higher stiffness, cells form shorter and more transient invadopodia and are less likely to extend invadopodia overall, contrasting with results from 2D studies. Subsequently, cell migration is diminished in stiff environments. Thus, although previous studies indicate that increased stiffness may promote malignant phenotypes and the degradative activity of invadopodia, our findings show that increased stiffness physically restricts invadopodia extension and cell migration in three-dimensional, BM-like environments.
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Registered trials
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