ZBTB18 inhibits SREBP-dependent lipid synthesis by halting CTBPs and LSD1 activity in glioblastoma.

Autor:	Ferrarese R; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Izzo A; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Andrieux G; Institute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany., Lagies S; Center for Biological Systems Analysis, University of Freiburg, Breisgau, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Bartmuss JP; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Masilamani AP; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Wasilenko A; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Osti D; Department of Experimental Oncology, IEO, European Institute of Oncology, IRCCS, Milan, Italy., Faletti S; Department of Experimental Oncology, IEO, European Institute of Oncology, IRCCS, Milan, Italy., Schulzki R; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Yuan S; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Kling E; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Ribecco V; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany., Heiland DH; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany., Tholen S; Institute of Clinical Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Prinz M; Institute of Neuropathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Signaling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Center for NeuroModulation (NeuroModul), University of Freiburg, Freiburg, Germany., Pelicci G; Department of Experimental Oncology, IEO, European Institute of Oncology, IRCCS, Milan, Italy.; Department of Translational Medicine, Piemonte Orientale University 'Amedeo Avo-Gadro,' Novara, Italy., Kammerer B; Center for Biological Systems Analysis, University of Freiburg, Breisgau, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.; BIOSS Centre of Biological Signaling Studies, University of Freiburg, Freiburg Germany., Boerries M; Institute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany., Carro MS; Department of Neurosurgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany maria.carro@uniklinik-freiburg.de.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2022 Nov 22; Vol. 6 (1). Date of Electronic Publication: 2022 Nov 22 (Print Publication: 2023).
DOI:	10.26508/lsa.202201400
Abstrakt:	Enhanced fatty acid synthesis is a hallmark of tumors, including glioblastoma. SREBF1/2 regulate the expression of enzymes involved in fatty acid and cholesterol synthesis. Yet, little is known about the precise mechanism regulating SREBP gene expression in glioblastoma. Here, we show that a novel interaction between the co-activator/co-repressor CTBP and the tumor suppressor ZBTB18 regulates the expression of SREBP genes. In line with our findings, metabolic assays and glucose tracing analysis confirm the reduction in several phospholipid species upon ZBTB18 expression. Our study identifies CTBP1/2 and LSD1 as co-activators of SREBP genes and indicates that the functional activity of the CTBP-LSD1 complex is altered by ZBTB18. ZBTB18 binding to the SREBP gene promoters is associated with reduced LSD1 demethylase activity of H3K4me2 and H3K9me2 marks. Concomitantly, the interaction between LSD1, CTBP, and ZNF217 is increased, suggesting that ZBTB18 promotes LSD1 scaffolding function. Our results outline a new epigenetic mechanism enrolled by ZBTB18 and its co-factors to regulate fatty acid synthesis that could be targeted to treat glioblastoma patients. (© 2022 Ferrarese et al.)
Databáze:	MEDLINE
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