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Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10258-63. doi: 10.1073/pnas.1222404110. Epub 2013 Jun 3.

MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells.

Author information

1
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Abstract

The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apoptosis, and neuronal differentiation in MYCN-amplified neuroblastoma cells and to increased survival of MYCN transgenic mice. We also report the discovery that inhibition of MYC is accompanied by accumulation of intracellular lipid droplets in tumor cells as a direct consequence of mitochondrial dysfunction. This study expands on the current knowledge of how MYC proteins control the metabolic reprogramming of cancer cells, especially highlighting lipid metabolism and the respiratory chain as important pathways involved in neuroblastoma pathogenesis. Together our data support direct MYC inhibition as a promising strategy for the treatment of MYC-driven tumors.

KEYWORDS:

cancer therapy; fatty acid oxidation; mitochondria; oxidative phosphorylation; small molecule

PMID:
23733953
PMCID:
PMC3690852
DOI:
10.1073/pnas.1222404110
[Indexed for MEDLINE]
Free PMC Article

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