Journal Article

DKFZ-2017-05925

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis.

Weigel, C. (First author)DKFZ* ; Veldwijk, M. R. ; Oakes, C. C.DKFZ* ; Seibold, P.DKFZ* ; Slynko, A.DKFZ* ; Liesenfeld, D. B.DKFZ* ; Rabionet, M.DKFZ* ; Hanke, S.DKFZ* ; Wenz, F. ; Sperk, E. ; Benner, A.DKFZ* ; Rösli, C.DKFZ* ; Sandhoff, R.DKFZ* ; Assenov, Y.DKFZ* ; Plass, C.DKFZ* ; Herskind, C. ; Chang-Claude, J.DKFZ* ; Schmezer, P.DKFZ* ; Popanda, O. (Last author)DKFZ*

2016
Nature Publishing Group London

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Please use a persistent id in citations: doi:10.1038/ncomms10893

Abstract: 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.

Keyword(s): EGR1 protein, human ; Early Growth Response Protein 1 ; RNA, Messenger ; Diacylglycerol Kinase

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Contributing Institute(s):

1. Epigenomik und Krebsrisikofaktoren (C010)
2. Epidemiologie von Krebserkrankungen (C020)
3. Biostatistik (C060)
4. Präventive Onkologie (G110)
5. AG Lipid-Pathobiochemie (G131)
6. Stammzellen und Krebs (A010)
7. HI-Stem (V960)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2016

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Database coverage:
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