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@ARTICLE{Thier:275768,
author = {A. C. Thier$^*$ and B. Di Marco$^*$ and E. Nevedomskaya and
B. Ulug$^*$ and R. Lesche and S. Christian and J.
Alfonso$^*$},
title = {{T}argeting fatty acid oxidation via {A}cyl-{C}o{A} binding
protein hinders glioblastoma invasion.},
journal = {Cell death $\&$ disease},
volume = {14},
number = {4},
issn = {2041-4889},
address = {London [u.a.]},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2023-00867},
pages = {296},
year = {2023},
note = {#EA:A230#LA:A230#},
abstract = {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.},
keywords = {Humans / Carrier Proteins: metabolism / Glioblastoma:
genetics / Diazepam Binding Inhibitor: metabolism / Lipid
Metabolism / Fatty Acids: metabolism / Carrier Proteins (NLM
Chemicals) / Diazepam Binding Inhibitor (NLM Chemicals) /
Fatty Acids (NLM Chemicals)},
cin = {A230},
ddc = {570},
cid = {I:(DE-He78)A230-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37120445},
pmc = {pmc:PMC10148872},
doi = {10.1038/s41419-023-05813-0},
url = {https://inrepo02.dkfz.de/record/275768},
}