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

2023-01Artigo científico Acesso aberto
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dc.contributor.authorRebelo, Ana R.
dc.contributor.authorHomem, Catarina C.F.
dc.contributor.authorC F Homem, Catarina
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutioniNOVA4Health - pólo NMS
dc.contributor.pblSpringer Science Business Media
dc.date.accessioned2023-01-13T22:20:43Z
dc.date.available2023-01-13T22:20:43Z
dc.date.issued2023-01
dc.descriptionFunding 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).
dc.description.abstractTumor 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent10415694
dc.identifier.doi10.1007/s00018-022-04668-6
dc.identifier.issn1420-682X
dc.identifier.otherPURE: 50439772
dc.identifier.otherPURE UUID: bdab6cf2-77cc-4db5-bcf7-ddb5f596d46e
dc.identifier.otherScopus: 85145701003
dc.identifier.otherPubMed: 36609617
dc.identifier.otherWOS: 000910155500001
dc.identifier.urihttp://hdl.handle.net/10362/147560
dc.identifier.urlhttps://www.scopus.com/pages/publications/85145701003
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAmino acid transporters
dc.subjectCancer
dc.subjectCD98 heavy chain
dc.subjectl-amino acid transporters (LATs)
dc.subjectMyc
dc.subjectNeural stem cell
dc.subjectMolecular Medicine
dc.subjectMolecular Biology
dc.subjectPharmacology
dc.subjectCellular and Molecular Neuroscience
dc.subjectCell Biology
dc.subjectSDG 3 - Good Health and Well-being
dc.titledMyc-dependent upregulation of CD98 amino acid transporters is required for Drosophila brain tumor growthen
dc.typejournal article
degois.publication.issue1
degois.publication.titleCellular and Molecular Life Sciences
degois.publication.volume80
dspace.entity.typePublication
person.familyNameHomem
person.givenNameCatarina
person.identifier.orcid0000-0003-4243-0298
rcaap.rightsopenAccess
relation.isAuthorOfPublicationd175310d-3f45-4446-a390-546a4d9a27ca
relation.isAuthorOfPublication.latestForDiscoveryd175310d-3f45-4446-a390-546a4d9a27ca

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