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Targeting fatty acid oxidation via Acyl-CoA binding protein hinders glioblastoma invasion

The 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 resul...

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Main Authors: Duman, Aset Ceren (Author) , Di Marco, Barbara (Author) , Nevedomskaya, Ekaterina (Author) , Ulug, Berk (Author) , Lesche, Ralf (Author) , Christian, Sven (Author) , Alfonso, Julieta (Author)
Format: Article (Journal)
Language:English
Published: 29 April 2023
In: Cell death & disease
Year: 2023, Volume: 14, Issue: 4, Pages: 1-11
ISSN:2041-4889
DOI:10.1038/s41419-023-05813-0
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41419-023-05813-0
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41419-023-05813-0
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Author Notes:Ceren Duman, Barbara Di Marco, Ekaterina Nevedomskaya, Berk Ulug, Ralf Lesche, Sven Christian and Julieta Alfonso
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Summary:The 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.
Item Description:Gesehen am 20.06.2023
Physical Description:Online Resource
ISSN:2041-4889
DOI:10.1038/s41419-023-05813-0

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