dc.contributor.author | Kreuzaler, P | |
dc.contributor.author | Inglese, P | |
dc.contributor.author | Ghanate, A | |
dc.contributor.author | Gjelaj, E | |
dc.contributor.author | Wu, V | |
dc.contributor.author | Panina, Y | |
dc.contributor.author | Mendez-Lucas, A | |
dc.contributor.author | MacLachlan, C | |
dc.contributor.author | Patani, N | |
dc.contributor.author | Hubert, CB | |
dc.contributor.author | Huang, H | |
dc.contributor.author | Greenidge, G | |
dc.contributor.author | Rueda, OM | |
dc.contributor.author | Taylor, AJ | |
dc.contributor.author | Karali, E | |
dc.contributor.author | Kazanc, E | |
dc.contributor.author | Spicer, A | |
dc.contributor.author | Dexter, A | |
dc.contributor.author | Lin, W | |
dc.contributor.author | Thompson, D | |
dc.contributor.author | Silva Dos Santos, M | |
dc.contributor.author | Calvani, E | |
dc.contributor.author | Legrave, N | |
dc.contributor.author | Ellis, JK | |
dc.contributor.author | Greenwood, W | |
dc.contributor.author | Green, M | |
dc.contributor.author | Nye, E | |
dc.contributor.author | Still, E | |
dc.contributor.author | CRUK Rosetta Grand Challenge Consortium | |
dc.contributor.author | Barry, S | |
dc.contributor.author | Goodwin, RJA | |
dc.contributor.author | Bruna, A | |
dc.contributor.author | Caldas, C | |
dc.contributor.author | MacRae, J | |
dc.contributor.author | de Carvalho, LPS | |
dc.contributor.author | Poulogiannis, G | |
dc.contributor.author | McMahon, G | |
dc.contributor.author | Takats, Z | |
dc.contributor.author | Bunch, J | |
dc.contributor.author | Yuneva, M | |
dc.coverage.spatial | Germany | |
dc.date.accessioned | 2024-01-30T10:59:26Z | |
dc.date.available | 2024-01-30T10:59:26Z | |
dc.date.issued | 2023-11-01 | |
dc.identifier | 10.1038/s42255-023-00915-7 | |
dc.identifier.citation | Nature Metabolism, 2023, 5 (11), pp. 1870 - 1886 | en_US |
dc.identifier.issn | 2522-5812 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6138 | |
dc.identifier.eissn | 2522-5812 | |
dc.identifier.eissn | 2522-5812 | |
dc.identifier.doi | 10.1038/s42255-023-00915-7 | |
dc.identifier.doi | 10.1038/s42255-023-00915-7 | |
dc.description.abstract | Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy1-3. Consequently, spatially resolved omics-level analyses are gaining traction4-9. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC, a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism10,11. Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B5) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets. | |
dc.format | Print-Electronic | |
dc.format.extent | 1870 - 1886 | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | NATURE PORTFOLIO | en_US |
dc.relation.ispartof | Nature Metabolism | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Animals | |
dc.subject | Female | |
dc.subject | Breast Neoplasms | |
dc.subject | Pantothenic Acid | |
dc.subject | Proto-Oncogene Proteins c-myc | |
dc.subject | Transcription Factors | |
dc.subject | Vitamins | |
dc.title | Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-09-28 | |
dc.date.updated | 2024-01-30T10:58:24Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1038/s42255-023-00915-7 | en_US |
rioxxterms.licenseref.startdate | 2023-11-01 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37946084 | |
pubs.issue | 11 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology/Preclinical Modelling of Paediatric Cancer Evolution | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1038/s42255-023-00915-7 | |
pubs.volume | 5 | |
icr.researchteam | Preclin Paed Cancer Evo | en_US |
icr.researchteam | Signalling Cancer Metab | en_US |
dc.contributor.icrauthor | Bruna Cabot, Alejandra | |
dc.contributor.icrauthor | Poulogiannis, Georgios | |
icr.provenance | Deposited by Mr Arek Surman on 2024-01-30. Deposit type is initial. No. of files: 1. Files: Vitamin Bsub5sub supports MYC oncogenic metabolism and tumor progression in breast cancer.pdf | |