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Type: Journal article
Title: Modulating the structure of EGFR with UV light: new possibilities in cancer therapy
Author: Correia, M.
Thiagarajan, V.
Coutinho, I.
Gajula, G.
Petersen, S.
Neves-Petersen, M.
Citation: PLoS One, 2014; 9(11):e111617-1-e111617-15
Publisher: Public Library of Science
Issue Date: 2014
ISSN: 1932-6203
Editor: Quaini, F.
Statement of
Manuel Correia, Viruthachalam Thiagarajan, Isabel Coutinho, Gnana Prakash Gajula, Steffen B. Petersen, Maria Teresa Neves-Petersen
Abstract: The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. EGFR is activated upon binding to e.g. epidermal growth factor (EGF), leading to cell survival, proliferation and migration. EGFR overactivation is associated with tumor progression. We have previously shown that low dose UVB illumination of cancer cells overexpressing EGFR prior to adding EGF halted the EGFR signaling pathway. We here show that UVB illumination of the extracellular domain of EGFR (sEGFR) induces protein conformational changes, disulphide bridge breakage and formation of tryptophan and tyrosine photoproducts such as dityrosine, N-formylkynurenine and kynurenine. Fluorescence spectroscopy, circular dichroism and thermal studies confirm the occurrence of conformational changes. An immunoassay has confirmed that UVB light induces structural changes in the EGF binding site. A monoclonal antibody which competes with EGF for binding sEGFR was used. We report clear evidence that UVB light induces structural changes in EGFR that impairs the correct binding of an EGFR specific antibody that competes with EGF for binding EGFR, confirming that the 3D structure of the EGFR binding domain suffered conformational changes upon UV illumination. The irradiance used is in the same order of magnitude as the integrated intensity in the solar UVB range. The new photonic technology disables a key receptor and is most likely applicable to the treatment of various types of cancer, alone or in combination with other therapies.
Rights: © 2014 Correia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI: 10.1371/journal.pone.0111617
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