Heterogeneity of the cancer cell line metabolic landscape

The unravelling of the complexity of cellular metabolism is in its infancy. Cancer-associated genetic alterations may result in changes to cellular metabolism that aid in understanding phenotypic changes, reveal detectable metabolic signatures, or elucidate vulnerabilities to particular drugs. To understand cancer-associated metabolic transformation, we performed untargeted metabolite analysis of 173 different cancer cell lines from 11 different tissues under constant conditions for 1,099 different species using mass spectrometry (MS). We correlate known cancer-associated mutations and gene expression programs with metabolic signatures, generating novel associations of known metabolic pathways with known cancer drivers. We show that metabolic activity correlates with drug sensitivity and use metabolic activity to predict drug response and synergy. Finally, we study the metabolic heterogeneity of cancer mutations across tissues, and find that genes exhibit a range of context specific, and more general metabolic control.

Automated summary

The understanding of cellular metabolism in cancer is still in its early stages. Genetic alterations associated with cancer may lead to changes in cellular metabolism, which can provide insight into phenotypic changes, identify detectable metabolic patterns, and reveal vulnerabilities to specific drugs. By analyzing the metabolites of 173 different cancer cell lines from 11 tissues, we were able to correlate known cancer-associated mutations and gene expression programs with metabolic signatures, establishing new connections between known metabolic pathways and cancer driver genes. We also discovered that metabolic activity is correlated with drug sensitivity, allowing us to predict drug response and synergy based on metabolic activity. Additionally, we investigated the metabolic heterogeneity of cancer mutations across tissues and found a range of context-specific and more general metabolic control in genes.