Using mass spectrometry imaging to dissect metabolic heterogeneity of tumours.

Session

Mass Spectrometry Imaging Across Length Scales in Life and Physical Sciences - Providing Atomic and Molecular Information

Authors

Dr Mariia Yuneva (1)

Affiliations

1. The Francis Crick Institute

Keywords

Tumour heterogeneity, correlative mass spectrometry imaging, stable isotopes, targetable biomarker

Abstract text

Among the factors presenting a challenge in designing metabolism-targeting anti-cancer therapies are flexibility of tumour metabolism and tumour heterogeneity. To identify metabolic vulnerabilities in the context of genetically heterogenous tumours we developed an integrated approach of correlative mass spectrometry imaging (MSI) that combines stable isotope tracing with light microscopy, electron microscopy and MSI. Using this approach, we identified pantothenic acid (Vitamin B5) as a key metabolite associated with high MYC expression and activity in both murine and human tumours. Areas of high MYC showed increased pantothenic acid uptake, resulting in higher levels of CoA and increased Krebs cycle activity. Mechanistically, we show that this is accomplished by Myc-mediated upregulation of multivitamin transporter SLC5A6.  Importantly depriving pantothenic acid from the diet reversed many MYC-mediated metabolic changes and reduced tumour growth demonstrating the importance of pantothenic acid metabolism as a targetable biomarker of MYC high tumour cells.