TY  - JOUR
AU  - Ruiz-Pérez, María Victoria
AU  - Sainero-Alcolado, Lourdes
AU  - Oliynyk, Ganna
AU  - Matuschek, Isabell
AU  - Balboni, Nicola
AU  - Ubhayasekera, S J Kumari A
AU  - Snaebjornsson, Marteinn Thor
AU  - Makowski, Kamil
AU  - Aaltonen, Kristina
AU  - Bexell, Daniel
AU  - Serra, Dolors
AU  - Nilsson, Roland
AU  - Bergquist, Jonas
AU  - Schulze, Almut
AU  - Arsenian-Henriksson, Marie
TI  - Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma.
JO  - iScience
VL  - 24
IS  - 2
SN  - 2589-0042
CY  - St. Louis
PB  - Elsevier
M1  - DKFZ-2021-00559
SP  - 102128
PY  - 2021
AB  - Many metabolic pathways, including lipid metabolism, are rewired in tumors to support energy and biomass production and to allow adaptation to stressful environments. Neuroblastoma is the second deadliest solid tumor in children. Genetic aberrations, as the amplification of the MYCN-oncogene, correlate strongly with disease progression. Yet, there are only a few molecular targets successfully exploited in the clinic. Here we show that inhibition of fatty acid synthesis led to increased neural differentiation and reduced tumor burden in neuroblastoma xenograft experiments independently of MYCN-status. This was accompanied by reduced levels of the MYCN or c-MYC oncoproteins and activation of ERK signaling. Importantly, the expression levels of genes involved in de novo fatty acid synthesis showed prognostic value for neuroblastoma patients. Our findings demonstrate that inhibition of de novo fatty acid synthesis is a promising pharmacological intervention strategy for the treatment of neuroblastoma independently of MYCN-status.
KW  - biological sciences (Other)
KW  - cancer (Other)
KW  - cell biology (Other)
KW  - molecular biology (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33659885
C2  - pmc:PMC7895756
DO  - DOI:10.1016/j.isci.2021.102128
UR  - https://inrepo02.dkfz.de/record/167797
ER  -