ArticleACS nano2025
Multivalent DNA Origami Enables Single-Molecule Dissection of Integrin αvβ6-Receptor Tyrosine Kinase Crosstalk in Cancer Biology.
Article in ACS nano, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Nucleic acid aptamers: new methods for selection, target validation, molecular diagnostics and therapeutics.Signal transduction and targeted therapy · 2026Review
- Mechanical Signaling From ECMs to Nuclear Envelopes in Cell Transitions and Fate Decisions: A Review and Perspective on Adhesion-Niche-Based Anti-EndMT and Anti-EMT.Annals of biomedical engineering · 2026Review
- Review
- Characterization of Non-Specific Electrostatic Interactions of Cationic Peptides with DNA Origami and Their Functional Consequences.Small methods · 2026Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nanoscale organization of integrin-mediated receptor crosstalk is crucial for controlling cellular signaling in cancer biology. Previously, interactions between integrin αvβ6 and receptor tyrosine kinases (RTKs) have been implicated in cancer progression, but the spatial regulatory mechanisms remain undefined. Here, we developed a programmable DNA origami-based platform for nanoscale control of heteroligand multivalency and spacing, enabling systematic investigation of αvβ6-RTK interactions in cancer biology. We identified a spatial activation threshold for the αvβ6-specific peptide A20FMDV2 that promotes A375P β6 cell adhesion and FAK phosphorylation along with spacing- and density-dependent EGFR phosphorylation triggered by EGFR aptamers. Importantly, at an optimized peptide-to-RTK (EGFR, HER2, and Met) aptamer ratio and ligand density, αvβ6-RTK coactivation synergistically enhanced cell spreading and amplified phosphorylation of AKT and ERK, part of the PI3K-AKT and Ras-MAPK pathways. Validation in breast cancer models (MDA-MB-468 and BT-474) highlighted cell-type-specific signaling dependencies. This platform offers a framework for tumor microenvironment mimics and integrin-RTK-targeted therapies, emphasizing the critical role of nanoscale ligand patterning and multivalency in cancer progression.
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