Modulating the structure of EGFR with UV light: new possibilities in cancer therapy.
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.
Department of Physics and Nanotechnology, Aalborg University, Aalborg, Denmark.
Manuel
M
Correia
BioPhotonics Group, Department of Nanomedicine, International Iberian Nanotechnology Laboratory (INL), Braga, Portugal; School of Chemistry, Bharathidasan University, Tiruchirappalli, India.
Viruthachalam
V
Thiagarajan
BioPhotonics Group, Department of Nanomedicine, International Iberian Nanotechnology Laboratory (INL), Braga, Portugal.
Isabel
I
Coutinho
BioPhotonics Group, Department of Nanomedicine, International Iberian Nanotechnology Laboratory (INL), Braga, Portugal.
Gnana Prakash
GP
Gajula
Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; The Institute for Lasers, Photonics and Biophotonics, University at Buffalo, The State University of New York, New York, United States of America.
Steffen B
SB
Petersen
BioPhotonics Group, Department of Nanomedicine, International Iberian Nanotechnology Laboratory (INL), Braga, Portugal. 2. BioPhotonics Group, Department of Nanomedicine, International Iberian Nanotechnology Laboratory (INL), Braga, Portugal and 6 Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, 9000 Aalborg, Denmark.
Maria Teresa
MT
Neves-Petersen
D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014467:Ultraviolet Therapy
D066246:ErbB Receptors