E-cadherin-mediated force transduction signals regulate global cell mechanics
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This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new integrin adhesions. This mechanism operates in addition to local cytoskeletal remodeling triggered by conformational changes in the E-cadherin-associated protein α-catenin, at sites of mechanical perturbation. Studies using magnetic twisting cytometry (MTC), together with traction force microscopy (TFM) and confocal imaging identified force-activated E-cadherin-specific signals that integrate cadherin force transduction, integrin activation and cell contractility. EGFR is required for the downstream activation of PI3K and myosin-II-dependent cell stiffening. Our findings also demonstrated that α-catenin-dependent cytoskeletal remodeling at perturbed E-cadherin adhesions does not require cell stiffening. These results broaden the repertoire of E-cadherin-based force transduction mechanisms, and define the force-sensitive signaling network underlying the mechano-chemical integration of spatially segregated adhesion receptors.
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EGFR activity status has been linked to intercellular junctional and actomyosin organization and function.
“As EGFR activity status has been linked to intercellular junctional and actomyosin organization and function26–29”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [28]
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Force Generation, Transmission, and Integration during Cell and Tissue Morphogenesis
Lecuit, T., Lenne, P.-F., & Munro, E. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100109-104027 · Cited by 621 · see citing works
Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces
Mertz, A. F., Che, Y., Banerjee, S., Goldstein, J. M., Rosowski, K. A., Revilla, S. F., Niessen, C. M., Marchetti, M. C., Dufresne, E. R., & Horsley, V. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217279110 · Cited by 243 · see citing works
α-Catenin cytomechanics – role in cadherin-dependent adhesion and mechanotransduction
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Cited by
Sorted by citations
Rübsam, M., Mertz, A. F., Kubo, A., Marg, S., Jüngst, C., Goranci-Buzhala, G., Schauss, A. C., Horsley, V., Dufresne, E. R., Moser, M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01170-7 · Cited by 210 · see citing works
Extracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells
Mierke, C. T. (2024) · Cells · doi:10.3390/cells13010096 · Cited by 146 · see citing works
- Authors
- Muhamed, I., Wu, J., Sehgal, P., Kong, X., Tajik, A., Wang, N., & Leckband, D. E.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2016-05-01
- Volume
- 129
- Issue
- 9
- Pages
- 1843-1854
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC4893802
- OpenAlex
- W2296441026
- Cited by
- 97
- References
- 3
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 9 · 2020: 8 · 2019: 7 · 2018: 12 · 2017: 15 · 2016: 4
- FWCI
- 8.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (R01 GM097443)
- National Science Foundation (1029871, 1462739)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Keywords
- E-cadherin, force transduction, cell mechanics, epidermal growth factor receptor, phosphatidylinositol 3-kinase, integrin-mediated adhesion, alpha-catenin, cytoskeletal remodeling, myosin II, cell contractility, mechanotransduction, magnetic twisting cytometry, traction force microscopy
- MeSH terms
- Animals, Cytoskeleton, Dogs, Humans, Cadherins, Mechanotransduction, Cellular, alpha Catenin, Madin Darby Canine Kidney Cells, MCF-7 Cells, ErbB Receptors
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