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

Hanna Zirath, Anna Frenzel, Ganna Oliynyk, Lova Segerstrom, Ulrica K. Westermark, Karin Larsson, Matilda Thorén, Kjell Hultenby, Janne Lehtio, Christer Einvik, Sven Påhlman, Per Kogner, Per-Johan Jakobsson, Marie Arsenian Henriksson

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)10258-10263
JournalProceedings of the National Academy of Sciences
Volume110
Issue number25
DOIs
Publication statusPublished - 2013

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Molecular Medicine (013031200)

Subject classification (UKÄ)

  • Cancer and Oncology

Free keywords

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

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