Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer.
Creators: name: Kreuzaler, Peter
name: Inglese, Paolo
name: Ghanate, Avinash
name: Gjelaj, Ersa
name: Wu, Vincen
name: Panina, Yulia
name: Mendez-Lucas, Andres
name: MacLachlan, Catherine
name: Patani, Neill
name: Hubert, Catherine B
name: Huang, Helen
name: Greenidge, Gina
name: Rueda, Oscar M
name: Taylor, Adam J
name: Karali, Evdoxia
name: Kazanc, Emine
name: Spicer, Amy
name: Dexter, Alex
name: Lin, Wei
name: Thompson, Daria
name: Dos Santos, Mariana Silva
name: Calvani, Enrica
name: Legrave, Nathalie
name: Ellis, James K
name: Greenwood, Wendy
name: Green, Mary
name: Nye, Emma
name: Still, Emma
name: Consortium, CRUK Rosetta Grand Challenge
name: Barry, Simon
name: Goodwin, Richard JA
name: Bruna, Alejandra
name: Caldas, Carlos
name: MacRae, James
name: de Carvalho, Luiz Pedro Sório
name: Poulogiannis, George
name: McMahon, Greg
name: Takats, Zoltan
name: Bunch, Josephine
name: Yuneva, Mariia
Publisher: name: The Francis Crick Institute
Year: 2023
Subjects: classificationCode: Tumour Biology
subject: Tumour Biology
classificationCode: Signalling & Oncogenes
subject: Signalling &amp; Oncogenes
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Infectious Disease
subject: Infectious Disease
classificationCode: Immunology
subject: Immunology
subject: FOS: Clinical medicine
classificationCode: Genetics & Genomics
subject: Genetics &amp; Genomics
classificationCode: Metabolism
subject: Metabolism
classificationCode: Developmental Biology
subject: Developmental Biology
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology
classificationCode: Genome Integrity & Repair
subject: Genome Integrity &amp; Repair
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Model organisms
subject: Model organisms
classificationCode: Biochemistry & Proteomics
subject: Biochemistry &amp; Proteomics
classificationCode: Structural Biology & Biophysics
subject: Structural Biology &amp; Biophysics
classificationCode: Cell Biology
subject: Cell Biology
classificationCode: Imaging
subject: Imaging

description: 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.