Comprehensive lipidome profiling to identify functional biomarkers of colorectal cancer metastasis
The onset and progression of various diseases, including cancer, are known to be associated with the disruption of lipid metabolism or signalling pathways. To date, however, systematic identification and quantification of the diverse range of individual molecular lipid species that may be present within cancerous cells or tissues, and exploration of their functional roles in malignancy and metastatic progression, have not been broadly explored.
In this project, we are applying a high-resolution 'shotgun' mass spectrometry based lipidome analysis strategy to systematically characterize and quantify >1000 individual lipids from a series of established cell culture models of primary and metastatic colorectal adenocarcinoma, and their secreted exosomes.
From this study, we are defining, for the first time, a core group of molecular lipid species (i.e., the 'cancer lipidome'), whose changes in abundance are highly correlated with colorectal cancer molecular phenotype and tumorigenic potential.
Then, we perform a series of targeted gene silencing experiments on specific enzymes involved in key lipid metabolism pathways, followed by molecular characterization at the proteome, lipidome and metabolome levels (i.e., 'multi-omics'), as well as functional proliferation, invasion, migration assays, to elucidate the as yet unknown functional role of colon cancer cell and exosome derived lipids in malignant transformation, metastatic progression and exosome mediated cancer signalling.
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