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

Author:
  • 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
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 Acad Sciences

Abstract 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.

Keywords

  • Cancer and Oncology
  • mitochondria
  • fatty acid oxidation
  • oxidative phosphorylation
  • small
  • molecule
  • cancer therapy

Other

Published
  • ISSN: 1091-6490
Sven Påhlman
E-mail: sven.pahlman [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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