MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells
Author
Summary, in English
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.
Department/s
- Department of Translational Medicine
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2013
Language
English
Pages
10258-10263
Publication/Series
Proceedings of the National Academy of Sciences
Volume
110
Issue
25
Document type
Journal article
Publisher
National Academy of Sciences
Topic
- Cancer and Oncology
Keywords
- mitochondria
- fatty acid oxidation
- oxidative phosphorylation
- small
- molecule
- cancer therapy
Status
Published
ISBN/ISSN/Other
- ISSN: 1091-6490