EGFR activation attenuates the mechanical threshold for integrin tension and focal adhesion formation
Autor: | Tejeshwar C. Rao, Victor Pui-Yan Ma, Alexa L. Mattheyses, Tara M. Urner, Aaron T. Blanchard, Khalid Salaita, Shreya Grandhi |
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Rok vydání: | 2020 |
Předmět: |
Focal Adhesions
Integrins 0303 health sciences biology Integrin Cell Cell Biology Adhesion Cell biology ErbB Receptors Extracellular matrix Focal adhesion 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Cell Adhesion biology.protein medicine Epidermal growth factor receptor Mechanotransduction Cell adhesion Research Article Signal Transduction 030304 developmental biology |
Zdroj: | J Cell Sci |
ISSN: | 1477-9137 0021-9533 |
DOI: | 10.1242/jcs.238840 |
Popis: | Mechanical forces, growth factors and the extracellular matrix all play crucial roles in cell adhesion. To understand how epidermal growth factor receptor (EGFR) impacts the mechanics of adhesion, we employed tension gauge tether (TGT) probes displaying the integrin ligand cRGDfK and quantified integrin tension. EGF exposure significantly increased spread area, cell circularity, integrated integrin tension, mechanical rupture density, radial organization and size of focal adhesions in Cos-7 cells on TGT surfaces. These findings suggest that EGFR regulates integrin tension and the spatial organization of focal adhesions. Additionally, we found that the mechanical tension threshold for outside-in integrin activation is tunable by EGFR. Parallel genetic and pharmacologic strategies demonstrated that these phenotypes are driven by ligand-dependent EGFR signaling. Our results establish a novel mechanism whereby EGFR regulates integrin activation and cell adhesion, providing control over cellular responses to the environment. This article has an associated First Person interview with the first author of the paper. |
Databáze: | OpenAIRE |
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