Nuclear EGFR renders cells radio-resistant by binding mRNA species and triggering a metabolic switch to increase lactate production

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
Klaus DittmannH Peter Rodemann

Abstract

EGFR is translocated into the cell nucleus in response to irradiation, where it is involved in regulation of radio-sensitivity. The aim of this study is to elucidate the functional role of nuclear EGFR. To identify EGFR-bound nuclear proteins and mRNAs, Maldi-TOF analysis and mRNA gene arrays were used. Complex formation of proteins was shown by confocal microscopy, immunoprecipitation and Western blotting. The effect of EGFR binding to mRNAs was exhibited by quantitative RT-PCR. Cellular endpoints were shown by Western blotting, mitochondrial mass quantification, lactate quantification and clonogenic survival assays. Maldi-TOF analysis of proteins bound to nuclear EGFR in response to irradiation showed colocalization with Lamin A and heterogeneous nuclear ribonucleoproteins. Confocal microscopy and Western blotting confirmed this colocalization. Both Lamin A and heterogeneous nuclear ribonucleoproteins are involved in mRNA processing. To support a role of nEGFR in this context after irradiation, we isolated EGFR-bound mRNA and observed an EGFR kinase-dependent mRNA stabilizing effect. With the help of DNA microarrays, we identified mRNAs associated with the Warburg effect that were bound to nuclear EGFR. In this context, we ob...Continue Reading

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Citations

Sep 20, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·H Peter Rodemann, Stephan Bodis
Apr 22, 2017·Cellular Signalling·Hongsen LiWeidong Han
May 19, 2018·International Journal of Radiation Biology·Poushali BhattacharyaAmit Kumar
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Jan 1, 2019·Chemical Research in Toxicology·Weili MiaoYinsheng Wang
Jun 23, 2019·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Xuezhu RongEnhua Wang

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