MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma
Summary: In pediatric neuroblastoma, MYCN-amplification correlates to poor clinical outcome and new treatment options are needed for these patients. Identifying the metabolic adaptations crucial for tumor progression may be a promising strategy to discover novel therapeutic targets. Here, we have co...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-11-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004219303992 |
| _version_ | 1818554173410508800 |
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| author | Ganna Oliynyk María Victoria Ruiz-Pérez Lourdes Sainero-Alcolado Johanna Dzieran Hanna Zirath Héctor Gallart-Ayala Craig E. Wheelock Henrik J. Johansson Roland Nilsson Janne Lehtiö Marie Arsenian-Henriksson |
| author_facet | Ganna Oliynyk María Victoria Ruiz-Pérez Lourdes Sainero-Alcolado Johanna Dzieran Hanna Zirath Héctor Gallart-Ayala Craig E. Wheelock Henrik J. Johansson Roland Nilsson Janne Lehtiö Marie Arsenian-Henriksson |
| author_sort | Ganna Oliynyk |
| collection | DOAJ |
| description | Summary: In pediatric neuroblastoma, MYCN-amplification correlates to poor clinical outcome and new treatment options are needed for these patients. Identifying the metabolic adaptations crucial for tumor progression may be a promising strategy to discover novel therapeutic targets. Here, we have combined proteomics, gene expression profiling, functional analysis, and metabolic tracing to decipher the impact of MYCN on neuroblastoma cell metabolism. We found that high MYCN levels are correlated with altered expression of proteins involved in multiple metabolic processes, including enhanced glycolysis and increased oxidative phosphorylation. Unexpectedly, we discovered that MYCN-amplified cells showed de novo glutamine synthesis. Furthermore, inhibition of β-oxidation reduced the viability of MYCN-amplified cells in vitro and decreased tumor burden in vivo, while not affecting non-MYCN–amplified tumors. Our data provide information on metabolic processes in MYCN expressing tumors, which could be exploited for the development of novel targeted therapies. : Biological Sciences; Cell Biology; Cancer Subject Areas: Biological Sciences, Cell Biology, Cancer |
| first_indexed | 2024-12-12T09:35:52Z |
| format | Article |
| id | doaj.art-30c5f535984240819ada19e400058301 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T09:35:52Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-30c5f535984240819ada19e4000583012022-12-22T00:28:43ZengElsevieriScience2589-00422019-11-0121188204MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting NeuroblastomaGanna Oliynyk0María Victoria Ruiz-Pérez1Lourdes Sainero-Alcolado2Johanna Dzieran3Hanna Zirath4Héctor Gallart-Ayala5Craig E. Wheelock6Henrik J. Johansson7Roland Nilsson8Janne Lehtiö9Marie Arsenian-Henriksson10Department of Microbiology, Tumor and Cell Biology (MTC), Biomedicum B7, Karolinska Institutet, 171 65 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology (MTC), Biomedicum B7, Karolinska Institutet, 171 65 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology (MTC), Biomedicum B7, Karolinska Institutet, 171 65 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology (MTC), Biomedicum B7, Karolinska Institutet, 171 65 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology (MTC), Biomedicum B7, Karolinska Institutet, 171 65 Stockholm, Sweden; The Dental and Pharmacological Benefits Agency, 104 22 Stockholm, SwedenDepartment of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, 171 65 Stockholm, Sweden; Metabolomics Unit, University of Lausanne – UNIL, Lausanne, SwitzerlandDepartment of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, 171 65 Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, 171 21 Solna, Sweden; Science for Life Laboratory, Cancer Proteomics Mass Spectrometry, 171 65 Stockholm, SwedenCenter for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden; Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden; Division of Cardiovascular Medicine, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, 171 21 Solna, Sweden; Science for Life Laboratory, Cancer Proteomics Mass Spectrometry, 171 65 Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology (MTC), Biomedicum B7, Karolinska Institutet, 171 65 Stockholm, Sweden; Corresponding authorSummary: In pediatric neuroblastoma, MYCN-amplification correlates to poor clinical outcome and new treatment options are needed for these patients. Identifying the metabolic adaptations crucial for tumor progression may be a promising strategy to discover novel therapeutic targets. Here, we have combined proteomics, gene expression profiling, functional analysis, and metabolic tracing to decipher the impact of MYCN on neuroblastoma cell metabolism. We found that high MYCN levels are correlated with altered expression of proteins involved in multiple metabolic processes, including enhanced glycolysis and increased oxidative phosphorylation. Unexpectedly, we discovered that MYCN-amplified cells showed de novo glutamine synthesis. Furthermore, inhibition of β-oxidation reduced the viability of MYCN-amplified cells in vitro and decreased tumor burden in vivo, while not affecting non-MYCN–amplified tumors. Our data provide information on metabolic processes in MYCN expressing tumors, which could be exploited for the development of novel targeted therapies. : Biological Sciences; Cell Biology; Cancer Subject Areas: Biological Sciences, Cell Biology, Cancerhttp://www.sciencedirect.com/science/article/pii/S2589004219303992 |
| spellingShingle | Ganna Oliynyk María Victoria Ruiz-Pérez Lourdes Sainero-Alcolado Johanna Dzieran Hanna Zirath Héctor Gallart-Ayala Craig E. Wheelock Henrik J. Johansson Roland Nilsson Janne Lehtiö Marie Arsenian-Henriksson MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma iScience |
| title | MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma |
| title_full | MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma |
| title_fullStr | MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma |
| title_full_unstemmed | MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma |
| title_short | MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma |
| title_sort | mycn enhanced oxidative and glycolytic metabolism reveals vulnerabilities for targeting neuroblastoma |
| url | http://www.sciencedirect.com/science/article/pii/S2589004219303992 |
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