Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer.

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.

Correction: Hopefully devoted to Q: targeting glutamine addiction in cancer.

This article was originally published under a CC BY NC SA License, but has now been made available under a CC BY 4.0 License.

Hopefully devoted to Q: targeting glutamine addiction in cancer.

Altered cell metabolism enables tumours to sustain their increased energetic and biosynthetic needs. Although tumour metabolism has long been considered a promising discipline in the development of cancer therapeutics, the majority of work has focused on changes in glucose metabolism. However, the complexity of cellular metabolism means that very rarely is an individual metabolite required for a single purpose, and thus understanding the overall metabolic requirements of tumours is vital. Over the past 30 years, increasing evidence has shown that many tumours require glutamine as well as glucose for their proliferation and survival. In this minireview, we explore the complexity of glutamine metabolism in tumour cells, discussing how the overall context of the tumour dictates the requirement for glutamine and how this can affect the design of effective therapeutic strategies.