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Non-Canonical Activation of the Epidermal Growth Factor Receptor by Carbon Nanoparticles

  • The epidermal growth factor receptor (EGFR) is an abundant membrane protein, which is essential for regulating many cellular processes including cell proliferation. In our earlier studies, we observed an activation of the EGFR and subsequent signaling events after the exposure of epithelial cells to carbon nanoparticles. In the current study, we describe molecular mechanisms that allow for discriminating carbon nanoparticle-specific from ligand-dependent receptor activation. Caveolin-1 is a key player that co-localizes with the EGFR upon receptor activation by carbon nanoparticles. This specific process mediated by nanoparticle-induced reactive oxygen species and the accumulation of ceramides in the plasma membrane is not triggered when cells are exposed to non-nano carbon particles or the physiological ligand EGF. The role of caveolae formation was demonstrated by the induction of higher order structures of caveolin-1 and by the inhibition of caveolae formation. Using an in vivo model with genetically modified mice lacking caveolin-1, it was possible to demonstrate that carbon nanoparticles in vivo trigger EGFR downstream signaling cascades via caveolin-1. The identified molecular mechanisms are, therefore, of toxicological relevance for inhaled nanoparticles. However, nanoparticles that are intentionally applied to humans might cause side effects depending on this phenomenon

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Document Type:Article
Author:Daniel Stöckmann, Tim Spannbrucker, Niloofar Ale-Agha, Philipp Jakobs, Christine Goy, Nadine Dyballa-Rukes, Tamara Hornstein, Alexander Kümper, Annette KraegelohORCiD, Judith Haendeler, Klaus UnfriedORCiD
Parent Title (English):Nanomaterials
First Page:267
Year of first Publication:2018
Release Date:2022/11/18
Tag:airway epithelium; caveolin-1; lung inflammation; protein kinase B; tyrosine kinase receptor
Impact:04.034 (2018)
Funding Information:Deutsche Forschungsgemeinschaft: individual grants UN110/4-1 and HA 2868/11-1 as well as from Research Training Group 1427)
Groups:Nano Zell Interaktionen
Open Access:Open Access
Signature:INM 2018/034
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International