Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma
Summary: Many metabolic pathways, including lipid metabolism, are rewired in tumors to support energy and biomass production and to allow adaptation to stressful environments. Neuroblastoma is the second deadliest solid tumor in children. Genetic aberrations, as the amplification of the MYCN-oncogen...
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doaj-fdcde282d39e41aa9c4af63f5a3e2e3b2021-02-21T04:35:39ZengElsevieriScience2589-00422021-02-01242102128Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastomaMaría Victoria Ruiz-Pérez0Lourdes Sainero-Alcolado1Ganna Oliynyk2Isabell Matuschek3Nicola Balboni4S.J. Kumari A. Ubhayasekera5Marteinn Thor Snaebjornsson6Kamil Makowski7Kristina Aaltonen8Daniel Bexell9Dolors Serra10Roland Nilsson11Jonas Bergquist12Almut Schulze13Marie Arsenian-Henriksson14Department of Microbiology, Tumor and Cell Biology (MTC), Biomedicum B7, Karolinska Institutet, 171 65 Stockholm, Sweden; Corresponding authorDepartment 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, SwedenAnalytical Chemistry, Department of Chemistry and Science for Life Laboratory, Uppsala University, 751 24 Uppsala, SwedenTumor Metabolism and Microenvironment, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDepartment of Inorganic and Organic Chemistry, Section of Organic Chemistry, Faculty of Chemistry, University of Barcelona, 08028 Barcelona, SpainTranslational Cancer Research, Lund University, 22381 Lund, SwedenTranslational Cancer Research, Lund University, 22381 Lund, SwedenDepartment of Biochemistry and Physiology, School of Pharmacy, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, 08028 Barcelona, Spain, and CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, SpainCardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Division of Cardiovascular Medicine, Karolinska University Hospital, 17176 Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, SwedenAnalytical Chemistry, Department of Chemistry and Science for Life Laboratory, Uppsala University, 751 24 Uppsala, SwedenTumor Metabolism and Microenvironment, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDepartment of Microbiology, Tumor and Cell Biology (MTC), Biomedicum B7, Karolinska Institutet, 171 65 Stockholm, Sweden; Corresponding authorSummary: Many metabolic pathways, including lipid metabolism, are rewired in tumors to support energy and biomass production and to allow adaptation to stressful environments. Neuroblastoma is the second deadliest solid tumor in children. Genetic aberrations, as the amplification of the MYCN-oncogene, correlate strongly with disease progression. Yet, there are only a few molecular targets successfully exploited in the clinic. Here we show that inhibition of fatty acid synthesis led to increased neural differentiation and reduced tumor burden in neuroblastoma xenograft experiments independently of MYCN-status. This was accompanied by reduced levels of the MYCN or c-MYC oncoproteins and activation of ERK signaling. Importantly, the expression levels of genes involved in de novo fatty acid synthesis showed prognostic value for neuroblastoma patients. Our findings demonstrate that inhibition of de novo fatty acid synthesis is a promising pharmacological intervention strategy for the treatment of neuroblastoma independently of MYCN-status.http://www.sciencedirect.com/science/article/pii/S2589004221000961biological sciencesmolecular biologycell biologycancer |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
María Victoria Ruiz-Pérez Lourdes Sainero-Alcolado Ganna Oliynyk Isabell Matuschek Nicola Balboni S.J. Kumari A. Ubhayasekera Marteinn Thor Snaebjornsson Kamil Makowski Kristina Aaltonen Daniel Bexell Dolors Serra Roland Nilsson Jonas Bergquist Almut Schulze Marie Arsenian-Henriksson |
spellingShingle |
María Victoria Ruiz-Pérez Lourdes Sainero-Alcolado Ganna Oliynyk Isabell Matuschek Nicola Balboni S.J. Kumari A. Ubhayasekera Marteinn Thor Snaebjornsson Kamil Makowski Kristina Aaltonen Daniel Bexell Dolors Serra Roland Nilsson Jonas Bergquist Almut Schulze Marie Arsenian-Henriksson Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma iScience biological sciences molecular biology cell biology cancer |
author_facet |
María Victoria Ruiz-Pérez Lourdes Sainero-Alcolado Ganna Oliynyk Isabell Matuschek Nicola Balboni S.J. Kumari A. Ubhayasekera Marteinn Thor Snaebjornsson Kamil Makowski Kristina Aaltonen Daniel Bexell Dolors Serra Roland Nilsson Jonas Bergquist Almut Schulze Marie Arsenian-Henriksson |
author_sort |
María Victoria Ruiz-Pérez |
title |
Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma |
title_short |
Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma |
title_full |
Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma |
title_fullStr |
Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma |
title_full_unstemmed |
Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma |
title_sort |
inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2021-02-01 |
description |
Summary: Many metabolic pathways, including lipid metabolism, are rewired in tumors to support energy and biomass production and to allow adaptation to stressful environments. Neuroblastoma is the second deadliest solid tumor in children. Genetic aberrations, as the amplification of the MYCN-oncogene, correlate strongly with disease progression. Yet, there are only a few molecular targets successfully exploited in the clinic. Here we show that inhibition of fatty acid synthesis led to increased neural differentiation and reduced tumor burden in neuroblastoma xenograft experiments independently of MYCN-status. This was accompanied by reduced levels of the MYCN or c-MYC oncoproteins and activation of ERK signaling. Importantly, the expression levels of genes involved in de novo fatty acid synthesis showed prognostic value for neuroblastoma patients. Our findings demonstrate that inhibition of de novo fatty acid synthesis is a promising pharmacological intervention strategy for the treatment of neuroblastoma independently of MYCN-status. |
topic |
biological sciences molecular biology cell biology cancer |
url |
http://www.sciencedirect.com/science/article/pii/S2589004221000961 |
work_keys_str_mv |
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