Abstract

Multiplatform Metabolomics of Oncogene Induced Senescence

Emily Armitage, Postdoc Researcher, Universidad San Pablo

Many studies have revealed that oncogenes impart an altered metabolic phenotype in cancer cells through the regulation of glycolysis, fatty acid metabolism and oxidative phosphorylation. Accumulating evidence suggests that RAS activation might be one of the key initiating events in tumour development. In normal cells, oncogene-induced senescence (OIS) is an anti-tumour mechanism of protection against cancer. To elucidate the role of this in normal cells we have designed a human fibroblast cell line with inducible H-RAS. Using this model, the metabolomic changes in response to H-RAS at different time points after induction were assessed though a multi-platform metabolic fingerprinting approach using GC-MS, LC-QTOF-MS and CE-TOF-MS. The transition of cells towards H-RAS OIS was marked by significant alterations in acyl carnitine, fatty acid and glycerophospholipid levels as well as alterations in central carbon metabolism and arginine and proline metabolism. A sequence of metabolic maps has been constructed that portrays the metabolic change over time, opening up new opportunities for fluxomics to highlight the relative importance of the pathways highlighted in the network. These results represent a considerable contribution has been made to understanding the connections between RAS and OIS in cancer.