Kreuzaler, P; Inglese, P; Ghanate, A; Gjelaj, E; Wu, V; Panina, Y; Mendez-Lucas, A; MacLachlan, C; Patani, N; Hubert, C B; Huang, H; Greenidge, G; Rueda, O M; Taylor, A J; Karali, E; Kazanc, E; Spicer, A; Dexter, A; Lin, W; Thompson, D; Silva Dos Santos, M; Calvani, E; Legrave, N; Ellis, J K; Greenwood, W; Green, M; Nye, E; Still, E; Kreuzaler, P; Barry, S; Goodwin, R J A; Bruna, A; Caldas, C; MacRae, J; de Carvalho, L P S; Poulogiannis, G; McMahon, G; Takats, Z; Bunch, J; Yuneva, M (2023) Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer. Nature Metabolism, 5 (11). pp. 1870-1886. ISSN 2522-5812

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Abstract

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy 1–3 . Consequently, spatially resolved omics-level analyses are gaining traction 4–9 . 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 metabolism 10,11 . Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B 5 ) 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.

Item Type:	Article
Subjects:	Nanoscience > Surface and Nanoanalysis
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1038/s42255-023-00915-7
Last Modified:	27 Oct 2026 14:54
URI:	https://npl.eprints-hosting.org/id/eprint/10579