ArticleProceedings of the National Academy of Sciences of the United States of America2021
Contractility, focal adhesion orientation, and stress fiber orientation drive cancer cell polarity and migration along wavy ECM substrates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 85 citations in OpenAlex.
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- Mesenchymal stromal/stem cells in tumour initiation, progression and therapy.Nature reviews. Cancer · 2026Review
- Colloid-patterned surfaces distinguish malignant mechanophenotypes.Materials today. Bio · 2026Article
- Melanoma/CSPG4-Enhanced Collagen-Mediated Contact Guidance Requires Mutant Active BRAF and the CSPG4 Core Protein Cytoplasmic Domain.Cellular and molecular bioengineering · 2026Article
- Molecular Mechanisms of Chondrocyte Hypertrophy Mediated by Physical Cues and Therapeutic Strategies in Osteoarthritis.International journal of molecular sciences · 2026Review
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- Interaction between CDC6 and Tmod3 accelerates resistance to paclitaxel through focal adhesion assembly.Signal transduction and targeted therapy · 2025Article
- Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion.bioRxiv : the preprint server for biology · 2025Article
- Enhanced Unidirectional Cell Migration Induced by Asymmetrical Micropatterns with Nanostructures.Journal of functional biomaterials · 2025Article
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- Review
- A Review of Talin- and Integrin-Dependent Molecular Mechanisms in Cancer Invasion and Metastasis.International journal of molecular sciences · 2025Review
- The role and regulation of integrins in cell migration and invasion.Nature reviews. Molecular cell biology · 2025Review
- Expansion limits of meshed split-thickness skin grafts.Acta biomaterialia · 2025Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Contact guidance is a powerful topographical cue that induces persistent directional cell migration. Healthy tissue stroma is characterized by a meshwork of wavy extracellular matrix (ECM) fiber bundles, whereas metastasis-prone stroma exhibit less wavy, more linear fibers. The latter topography correlates with poor prognosis, whereas more wavy bundles correlate with benign tumors. We designed nanotopographic ECM-coated substrates that mimic collagen fibril waveforms seen in tumors and healthy tissues to determine how these nanotopographies may regulate cancer cell polarization and migration machineries. Cell polarization and directional migration were inhibited by fibril-like wave substrates above a threshold amplitude. Although polarity signals and actin nucleation factors were required for polarization and migration on low-amplitude wave substrates, they did not localize to cell leading edges. Instead, these factors localized to wave peaks, creating multiple "cryptic leading edges" within cells. On high-amplitude wave substrates, retrograde flow from large cryptic leading edges depolarized stress fibers and focal adhesions and inhibited cell migration. On low-amplitude wave substrates, actomyosin contractility overrode the small cryptic leading edges and drove stress fiber and focal adhesion orientation along the wave axis to mediate directional migration. Cancer cells of different intrinsic contractility depolarized at different wave amplitudes, and cell polarization response to wavy substrates could be tuned by manipulating contractility. We propose that ECM fibril waveforms with sufficiently high amplitude around tumors may serve as "cell polarization barriers," decreasing directional migration of tumor cells, which could be overcome by up-regulation of tumor cell contractility.
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