dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth

Detalhes bibliográficos
Autor(a) principal: Rebelo, Ana R.
Data de Publicação: 2023
Outros Autores: Homem, Catarina C.F.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/147560
Resumo: Funding Information: We would like to thank Tiago Baptista and Hugo Silva for experimental help. We thank Florence Janody and Rita Teodoro for critical reading of the manuscript. We thank Juergen Knoblich for the Miranda antibody. We thank the cytometry and fly facilities at NOVA Medical School for technical support and CONGENTO: consortium for genetically tractable organisms (LISBOA-01-0145-FEDER-022170); Bloomington Drosophila Stock Center (NIH P40OD018537) and Vienna Drosophila Resource Center (VDRC) [52 ], for the stocks used in this study; the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. Funding Information: Open access funding provided by FCT|FCCN (b-on). This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2017-STG-GA 759853-StemCellHabitat); by Wellcome Trust and Howard Hughes Medical Institute (HHMI-208581/Z/17/Z-Metabolic Reg SC fate); EMBO Installation grant (H2020-EMBO-3311/2017/G2017) and by Fundação para a Ciência e Tecnologia (IF/01265/2014/CP1252/CT0004, EXPL/BIA-BID/1394/2021 and 2020.05639.BD to A.R.R). This work was supported by iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, and by the Associated Laboratory LS4FUTURE (LA/P/0087/2020), two programs financially supported by Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior. Publisher Copyright: © 2023, The Author(s).
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spelling dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growthAmino acid transportersCancerCD98 heavy chainl-amino acid transporters (LATs)MycNeural stem cellMolecular MedicineMolecular BiologyPharmacologyCellular and Molecular NeuroscienceCell BiologySDG 3 - Good Health and Well-beingFunding Information: We would like to thank Tiago Baptista and Hugo Silva for experimental help. We thank Florence Janody and Rita Teodoro for critical reading of the manuscript. We thank Juergen Knoblich for the Miranda antibody. We thank the cytometry and fly facilities at NOVA Medical School for technical support and CONGENTO: consortium for genetically tractable organisms (LISBOA-01-0145-FEDER-022170); Bloomington Drosophila Stock Center (NIH P40OD018537) and Vienna Drosophila Resource Center (VDRC) [52 ], for the stocks used in this study; the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. Funding Information: Open access funding provided by FCT|FCCN (b-on). This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2017-STG-GA 759853-StemCellHabitat); by Wellcome Trust and Howard Hughes Medical Institute (HHMI-208581/Z/17/Z-Metabolic Reg SC fate); EMBO Installation grant (H2020-EMBO-3311/2017/G2017) and by Fundação para a Ciência e Tecnologia (IF/01265/2014/CP1252/CT0004, EXPL/BIA-BID/1394/2021 and 2020.05639.BD to A.R.R). This work was supported by iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, and by the Associated Laboratory LS4FUTURE (LA/P/0087/2020), two programs financially supported by Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior. Publisher Copyright: © 2023, The Author(s).Tumor cells have an increased demand for nutrients to sustain their growth, but how these increased metabolic needs are ensured or how this influences tumor formation and progression remains unclear. To unravel tumor metabolic dependencies, particularly from extracellular metabolites, we have analyzed the role of plasma membrane metabolic transporters in Drosophila brain tumors. Using a well-established neural stem cell-derived tumor model, caused by brat knockdown, we have found that 13 plasma membrane metabolic transporters, including amino acid, carbohydrate and monocarboxylate transporters, are upregulated in tumors and are required for tumor growth. We identified CD98hc and several of the light chains with which it can form heterodimeric amino acid transporters, as crucial players in brat RNAi (bratIR) tumor progression. Knockdown of these components of CD98 heterodimers caused a dramatic reduction in tumor growth. Our data also reveal that the oncogene dMyc is required and sufficient for the upregulation of CD98 transporter subunits in these tumors. Furthermore, tumor-upregulated dmyc and CD98 transporters orchestrate the overactivation of the growth-promoting signaling pathway TOR, forming a core growth regulatory network to support brat IR tumor progression. Our findings highlight the important link between oncogenes, metabolism, and signaling pathways in the regulation of tumor growth and allow for a better understanding of the mechanisms necessary for tumor progression.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)iNOVA4Health - pólo NMSRUNRebelo, Ana R.Homem, Catarina C.F.2023-01-13T22:20:43Z2023-012023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/147560eng1420-682XPURE: 50439772https://doi.org/10.1007/s00018-022-04668-6info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:28:47Zoai:run.unl.pt:10362/147560Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:53:00.219430Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth
title dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth
spellingShingle dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth
Rebelo, Ana R.
Amino acid transporters
Cancer
CD98 heavy chain
l-amino acid transporters (LATs)
Myc
Neural stem cell
Molecular Medicine
Molecular Biology
Pharmacology
Cellular and Molecular Neuroscience
Cell Biology
SDG 3 - Good Health and Well-being
title_short dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth
title_full dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth
title_fullStr dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth
title_full_unstemmed dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth
title_sort dMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growth
author Rebelo, Ana R.
author_facet Rebelo, Ana R.
Homem, Catarina C.F.
author_role author
author2 Homem, Catarina C.F.
author2_role author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
iNOVA4Health - pólo NMS
RUN
dc.contributor.author.fl_str_mv Rebelo, Ana R.
Homem, Catarina C.F.
dc.subject.por.fl_str_mv Amino acid transporters
Cancer
CD98 heavy chain
l-amino acid transporters (LATs)
Myc
Neural stem cell
Molecular Medicine
Molecular Biology
Pharmacology
Cellular and Molecular Neuroscience
Cell Biology
SDG 3 - Good Health and Well-being
topic Amino acid transporters
Cancer
CD98 heavy chain
l-amino acid transporters (LATs)
Myc
Neural stem cell
Molecular Medicine
Molecular Biology
Pharmacology
Cellular and Molecular Neuroscience
Cell Biology
SDG 3 - Good Health and Well-being
description Funding Information: We would like to thank Tiago Baptista and Hugo Silva for experimental help. We thank Florence Janody and Rita Teodoro for critical reading of the manuscript. We thank Juergen Knoblich for the Miranda antibody. We thank the cytometry and fly facilities at NOVA Medical School for technical support and CONGENTO: consortium for genetically tractable organisms (LISBOA-01-0145-FEDER-022170); Bloomington Drosophila Stock Center (NIH P40OD018537) and Vienna Drosophila Resource Center (VDRC) [52 ], for the stocks used in this study; the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. Funding Information: Open access funding provided by FCT|FCCN (b-on). This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2017-STG-GA 759853-StemCellHabitat); by Wellcome Trust and Howard Hughes Medical Institute (HHMI-208581/Z/17/Z-Metabolic Reg SC fate); EMBO Installation grant (H2020-EMBO-3311/2017/G2017) and by Fundação para a Ciência e Tecnologia (IF/01265/2014/CP1252/CT0004, EXPL/BIA-BID/1394/2021 and 2020.05639.BD to A.R.R). This work was supported by iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, and by the Associated Laboratory LS4FUTURE (LA/P/0087/2020), two programs financially supported by Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior. Publisher Copyright: © 2023, The Author(s).
publishDate 2023
dc.date.none.fl_str_mv 2023-01-13T22:20:43Z
2023-01
2023-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/147560
url http://hdl.handle.net/10362/147560
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1420-682X
PURE: 50439772
https://doi.org/10.1007/s00018-022-04668-6
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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