TY  - JOUR
AU  - Weigel, Christoph
AU  - Veldwijk, Marlon R
AU  - Oakes, Christopher C
AU  - Seibold, Petra
AU  - Slynko, Alla
AU  - Liesenfeld, David B
AU  - Rabionet, Mariona
AU  - Hanke, Sabrina
AU  - Wenz, Frederik
AU  - Sperk, Elena
AU  - Benner, Axel
AU  - Rösli, Christoph
AU  - Sandhoff, Roger
AU  - Assenov, Yassen
AU  - Plass, Christoph
AU  - Herskind, Carsten
AU  - Chang-Claude, Jenny
AU  - Schmezer, Peter
AU  - Popanda, Odilia
TI  - Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis.
JO  - Nature Communications
VL  - 7
IS  - NN
SN  - 2041-1723
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2017-05925
SP  - 10893 -
PY  - 2016
AB  - 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.
KW  - EGR1 protein, human (NLM Chemicals)
KW  - Early Growth Response Protein 1 (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - Diacylglycerol Kinase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26964756
C2  - pmc:PMC4792958
DO  - DOI:10.1038/ncomms10893
UR  - https://inrepo02.dkfz.de/record/130847
ER  -