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The landscape of cancer cell line metabolism

2019; Nature Portfolio; Volume: 25; Issue: 5 Linguagem: Inglês

10.1038/s41591-019-0404-8

1546-170X

Haoxin Li, Shaoyang Ning, Mahmoud Ghandi, Gregory V. Kryukov, Shuba Gopal, Amy Deik, Amanda Souza, Kerry A. Pierce, Paula Keskula, Desiree Hernandez, Julie Ann, Dojna Shkoza, Verena Apfel, Yilong Zou, Francisca Vázquez, Jordi Barretina, Raymond Pagliarini, Giorgio Giacomo Galli, David E. Root, William C. Hahn, Aviad Tsherniak, Marios Giannakis, Stuart L. Schreiber, Clary B. Clish, Levi A. Garraway, William R. Sellers,

Diet and metabolism studies

Despite considerable efforts to identify cancer metabolic alterations that might unveil druggable vulnerabilities, systematic characterizations of metabolism as it relates to functional genomic features and associated dependencies remain uncommon. To further understand the metabolic diversity of cancer, we profiled 225 metabolites in 928 cell lines from more than 20 cancer types in the Cancer Cell Line Encyclopedia (CCLE) using liquid chromatography-mass spectrometry (LC-MS). This resource enables unbiased association analysis linking the cancer metabolome to genetic alterations, epigenetic features and gene dependencies. Additionally, by screening barcoded cell lines, we demonstrated that aberrant ASNS hypermethylation sensitizes subsets of gastric and hepatic cancers to asparaginase therapy. Finally, our analysis revealed distinct synthesis and secretion patterns of kynurenine, an immune-suppressive metabolite, in model cancer cell lines. Together, these findings and related methodology provide comprehensive resources that will help clarify the landscape of cancer metabolism.