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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Påhlman, Sven Zirath, Hanna Frenzel, Anna Lehtiö, Janne Larsson, Karin Kogner, Per Segerström, Lova Jakobsson, Per-johan Westermark, Ulrica K. Einvik, Christer Oliynyk, Ganna Henriksson, Marie Arsenian Munksgaard Persson, Matilda Hultenby, Kjell |
| Description | Author Affiliation: Zirath H ( 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 25 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Drug Effects Lipid Metabolism Neuroblastoma Drug Therapy Proto-Oncogene Proteins C-myc Antagonists & Inhibitors Thiazoles Pharmacology Animals Antineoplastic Agents Cell Differentiation Cell Line, Tumor Cell Proliferation Disease Models, Animal Electron Transport Fatty Acids Metabolism Mice Mice, Nude Mice, Transgenic Mitochondria Pathology Receptor, TrkA Signal Transduction Xenograft Model Antitumor Assays Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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