MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells
Författare
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.
Avdelning/ar
- Institutionen för translationell medicin
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2013
Språk
Engelska
Sidor
10258-10263
Publikation/Tidskrift/Serie
Proceedings of the National Academy of Sciences
Volym
110
Issue
25
Dokumenttyp
Artikel i tidskrift
Förlag
National Academy of Sciences
Ämne
- Cancer and Oncology
Nyckelord
- mitochondria
- fatty acid oxidation
- oxidative phosphorylation
- small
- molecule
- cancer therapy
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1091-6490