Journal Article DKFZ-2021-00559

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Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma.

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2021
Elsevier St. Louis

iScience 24(2), 102128 () [10.1016/j.isci.2021.102128]
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Abstract: 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.

Keyword(s): biological sciences ; cancer ; cell biology ; molecular biology

Classification:

Contributing Institute(s):
  1. Tumor Metabolismus und Microenvironment (A410)
Research Program(s):
  1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2021
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Medline ; Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND (No Version) ; DOAJ ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2021-03-08, last modified 2024-02-29


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