摘要：SummaryMany 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 theMYCN-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 ofMYCN-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 inde novofatty acid synthesis showed prognostic value for neuroblastoma patients. Our findings demonstrate that inhibition ofde novofatty acid synthesis is a promising pharmacological intervention strategy for the treatment of neuroblastoma independently ofMYCN-status.Graphical AbstractDisplay OmittedHighlights•Fatty acid synthesis inhibition reduces neuroblastoma growthin vitroandin vivo•Decreased availability or reduced lipid synthesis downregulates MYC levels•Impaired fatty acid synthesis induces neural differentiation through ERK activation•High expression of fatty-acid-synthesis-related genes correlates with bad prognosisBiological sciences; molecular biology; cell biology; cancer
