Premium
Mapping Lipid Networks in Cancer by Integrated Proteomics and Metabolomics
Author(s) -
Cravatt Benjamin F.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a93-e
Subject(s) - metabolomics , proteomics , computational biology , biology , cancer cell , proteome , cancer , metabolic pathway , enzyme , bioinformatics , biochemistry , gene , genetics
Breakthroughs in the diagnosis and treatment of cancer depend on the discovery of new biomarkers and therapeutic targets for this disease. Toward this end, global molecular profiling methods hold great promise, as they provide a relatively unbiased portrait of the biochemical composition of cancer cells and can reveal unanticipated alterations in their metabolic and signaling networks. Nonetheless, the identification and functional characterization of enzymatic pathways that support cancer pathogenesis have, to date, been hindered by a lack of “systems biology” techniques that can evaluate their activity in complex biological samples. To address this problem, we have introduced functional proteomic and metabolomic technologies termed activity‐based protein profiling (ABPP) and discovery metabolite profiling (DMP), respectively. ABPP, which utilizes active site‐directed chemical probes to determine the functional state of large numbers of enzymes directly in whole proteomes, has enabled the discovery of enzyme activities that are elevated in aggressive cancer cells and tumors. DMP, which constitutes a global, untargeted method to characterize metabolic fluxes, has facilitated the discovery of natural substrates for known and novel cancer‐related enzymes. In this presentation, I will discuss our group's progress towards uniting the ABPP and DMP methods to an integrated platform for the global analysis of biochemical pathways altered in human cancer cells. Specifically, I will discuss: 1) the identification of enzyme activities and lipid metabolites that are elevated in aggressive cancer cells, and 2) the integration of these enzymes and small molecules into networks and our efforts to test the function of these biochemical pathways in cancer pathogenesis.