Next Article in Journal
ZnO Nanostructures for Drug Delivery and Theranostic Applications
Previous Article in Journal
Electrodes Based on Carbon Aerogels Partially Graphitized by Doping with Transition Metals for Oxygen Reduction Reaction
Previous Article in Special Issue
Implementation of Safe-by-Design for Nanomaterial Development and Safe Innovation: Why We Need a Comprehensive Approach
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle

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

IUF—Leibniz-Institut für Umweltmedizinische Forschung, Auf’m Hennekamp 50, 40225 Düsseldorf, Germany
INM—Leibniz-Institut für Neue Materialien, Campus D2 2, 66123 Saarbrücken, Germany
Medizinische Fakultät, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany
Author to whom correspondence should be addressed.
Those authors contributed equally to this work.
Nanomaterials 2018, 8(4), 267;
Received: 25 February 2018 / Revised: 13 April 2018 / Accepted: 16 April 2018 / Published: 23 April 2018
(This article belongs to the Special Issue Nanosafety 2017)
PDF [1250 KB, uploaded 3 May 2018]


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. View Full-Text
Keywords: tyrosine kinase receptor; caveolin-1; airway epithelium; lung inflammation; protein kinase B tyrosine kinase receptor; caveolin-1; airway epithelium; lung inflammation; protein kinase B

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Stöckmann, D.; Spannbrucker, T.; Ale-Agha, N.; Jakobs, P.; Goy, C.; Dyballa-Rukes, N.; Hornstein, T.; Kümper, A.; Kraegeloh, A.; Haendeler, J.; Unfried, K. Non-Canonical Activation of the Epidermal Growth Factor Receptor by Carbon Nanoparticles. Nanomaterials 2018, 8, 267.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Nanomaterials EISSN 2079-4991 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top