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000275768 245__ $$aTargeting fatty acid oxidation via Acyl-CoA binding protein hinders glioblastoma invasion.
000275768 260__ $$aLondon [u.a.]$$bNature Publishing Group$$c2023
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000275768 520__ $$aThe diffuse nature of Glioblastoma (GBM) tumors poses a challenge to current therapeutic options. We have previously shown that Acyl-CoA Binding Protein (ACBP, also known as DBI) regulates lipid metabolism in GBM cells, favoring fatty acid oxidation (FAO). Here we show that ACBP downregulation results in wide transcriptional changes affecting invasion-related genes. In vivo experiments using patient-derived xenografts combined with in vitro models demonstrated that ACBP sustains GBM invasion via binding to fatty acyl-CoAs. Blocking FAO mimics ACBPKD-induced immobility, a cellular phenotype that can be rescued by increasing FAO rates. Further investigation into ACBP-downstream pathways served to identify Integrin beta-1, a gene downregulated upon inhibition of either ACBP expression or FAO rates, as a mediator for ACBP's role in GBM invasion. Altogether, our findings highlight a role for FAO in GBM invasion and reveal ACBP as a therapeutic vulnerability to stall FAO and subsequent cell invasion in GBM tumors.
000275768 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000275768 650_7 $$2NLM Chemicals$$aCarrier Proteins
000275768 650_7 $$2NLM Chemicals$$aDiazepam Binding Inhibitor
000275768 650_7 $$2NLM Chemicals$$aFatty Acids
000275768 650_2 $$2MeSH$$aHumans
000275768 650_2 $$2MeSH$$aCarrier Proteins: metabolism
000275768 650_2 $$2MeSH$$aGlioblastoma: genetics
000275768 650_2 $$2MeSH$$aDiazepam Binding Inhibitor: metabolism
000275768 650_2 $$2MeSH$$aLipid Metabolism
000275768 650_2 $$2MeSH$$aFatty Acids: metabolism
000275768 7001_ $$0P:(DE-He78)3f238cb47096916308d99eabbce682e9$$aDi Marco, Barbara$$b1$$eFirst author$$udkfz
000275768 7001_ $$aNevedomskaya, Ekaterina$$b2
000275768 7001_ $$0P:(DE-He78)5a85b6e269e83210863fec67ef9fd8b8$$aUlug, Berk$$b3
000275768 7001_ $$aLesche, Ralf$$b4
000275768 7001_ $$aChristian, Sven$$b5
000275768 7001_ $$0P:(DE-He78)3f128e570b3a9009d7b52a0523af43dd$$aAlfonso, Julieta$$b6$$eLast author$$udkfz
000275768 773__ $$0PERI:(DE-600)2541626-1$$a10.1038/s41419-023-05813-0$$gVol. 14, no. 4, p. 296$$n4$$p296$$tCell death & disease$$v14$$x2041-4889$$y2023
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