Journal article
Acyl-CoA-Binding Protein Drives Glioblastoma Tumorigenesis by Sustaining Fatty Acid Oxidation
Ceren Duman, Kaneschka Yaqubi, Angelika Hoffmann, Azer Aylin Acikgoz, Andrey Korshunov, Martin Bendszus, Christel Herold-Mende, Hai-Kun Liu, Julieta Alfonso
CELL METABOLISM | CELL PRESS | Published : 2019
Abstract
Glioblastoma multiforme (GBM) undergoes metabolic reprogramming to meet the high ATP and anabolic demands of the tumor cells. However, the role of fatty acid oxidation (FAO) and its regulators in the GBM context has been largely unknown. Here, we show that the neural stem cell pro-proliferative factor acyl-CoA-binding protein (ACBP, also known as DBI) is highly expressed in GBM, and by binding to acyl-CoAs, it cell-autonomously maintains high proliferation rates, promoting tumor growth and poor survival in several preclinical models. Mechanistic experiments using ACBP-acyl-CoA binding affinity variants and pharmacological FAO modulators suggest that ACBP supports tumor growth by controlling ..
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Awarded by German Federal Ministry of Education and Research
Funding Acknowledgements
We thank Damir Krunic (DKFZ Light Microscopy core facility) for assistance in microscopy and ImageJ scripts; Steffen Schmidt (DKFZ Flow Cytometry and FACS core facility) for assistance in flow cytometry and analysis; Melanie Lutz, Fabian Uch, and Manuel Fischer for excellent technical assistance; Lasse Meyer for helping with in vitro experiments; Annika Zota and Prof. Stefan Herzig (Heidelberg University Hospital) for kindly providing support with Seahorse Metabolic Analyzer experiments; Prof. Nils Faergeman (University of Southern Denmark) for kindly providing the bovine ACBP mutant variants; Prof. Susanne Mandrup (University of Southern Denmark) for kindly providing the ACBP-floxed mice; Prof. Hannah Monyer for providing input regarding electrophysiological experiments; and Dr. Erik Jung and Prof. Frank Winkler for critical reading of the manuscript. This work was supported by the German Federal Ministry of Education and Research (BMBF 01GQ1405 to J.A.).