%0 Journal Article
%A Weigel, Christoph
%A Veldwijk, Marlon R
%A Oakes, Christopher C
%A Seibold, Petra
%A Slynko, Alla
%A Liesenfeld, David B
%A Rabionet, Mariona
%A Hanke, Sabrina
%A Wenz, Frederik
%A Sperk, Elena
%A Benner, Axel
%A Rösli, Christoph
%A Sandhoff, Roger
%A Assenov, Yassen
%A Plass, Christoph
%A Herskind, Carsten
%A Chang-Claude, Jenny
%A Schmezer, Peter
%A Popanda, Odilia
%T Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis.
%J Nature Communications
%V 7
%N NN
%@ 2041-1723
%C London
%I Nature Publishing Group
%M DKFZ-2017-05925
%P 10893 -
%D 2016
%X Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (DGKA). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced DGKA transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy.
%K EGR1 protein, human (NLM Chemicals)
%K Early Growth Response Protein 1 (NLM Chemicals)
%K RNA, Messenger (NLM Chemicals)
%K Diacylglycerol Kinase (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:26964756
%2 pmc:PMC4792958
%R 10.1038/ncomms10893
%U https://inrepo02.dkfz.de/record/130847