肿瘤本质上具有异质性，并且众所周知，这指导了它们的进化，阻碍了它们的分类并阻碍了治疗1-3。因此，空间解析的组学水平分析正在获得关注4-9。尽管治疗兴趣很大，但肿瘤代谢一直落后于这一发展，并且缺乏有关其空间组织的数据。为了解决这一缺点，我们着手研究癌基因 c-MYC 的局部代谢效应，c-MYC 是一种多效性转录因子，随着肿瘤进展而积累并影响代谢10,11。通过相关质谱成像，我们发现泛酸（维生素 B5）与人类和小鼠乳腺肿瘤内的 MYC 高区域相关，在该区域泛酸转化为辅酶 A 促进克雷布斯循环活动。从机制上讲，我们表明这是通过 MYC 介导的多种维生素转运蛋白 SLC5A6 的上调来实现的。值得注意的是，我们发现单独 SLC5A6 过度表达可以诱导细胞生长增加和向生物合成的转变，而相反，泛酸的饮食限制会导致许多 MYC 介导的代谢变化逆转，并导致肿瘤生长受到阻碍。因此，我们的工作将维生素和辅因子的可用性确定为肿瘤进展的潜在瓶颈，可以在治疗上加以利用。总体而言，我们表明对局部代谢的空间理解有助于识别临床相关的、易于处理的代谢目标。© 2023。作者。

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.© 2023. The Author(s).