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Fatty acid synthesis in colorectal cancer: characterization of lipid metabolism in serum, tumour, and normal host tissues

ABSTRACT: The objective of the experiment was to compare serum fatty acid metabolite abundance between individuals with varying clinical stages of colorectal cancer (stage I-IV) and age-and-gender matched disease-free controls. Fatty acid metabolite abundance was compared between locoregional (stage I-III) and liver metastatic (stage IV) cancer, as well as between all stages of colorectal cancer (stage I-IV) and disease-free controls. Reprogrammed energy metabolism is now listed as one of the central hallmarks of cancer cells. Aberrant fatty acid metabolism contributes to tumourigenesis through provision of substrates for membrane synthesis, signalling molecules, and synthesis of complex lipids. In this thesis, the role of fatty acid metabolism is explored in the context of colorectal cancer. Metabolomics techniques were employed to characterize fatty acid metabolites in serum, and lipogenic gene expression was quantified in tumour and normal tissues to investigate host response to cancer. Fatty acid metabolite abundance was increased in the serum of individuals with colorectal cancer, and a growth factor signalling axis and lipogenic transcription factor upstream of the endogenous fatty acid synthesis pathway were increased in colorectal liver metastases. It was concluded that liver metastases have an effect on growth factor production in the hepatic microenvironment, leading to increased signalling through a pathway that activates the lipogenic transcription factor that regulates fatty acid synthesis.

INSTRUMENT(S): GCT Premier (Waters)

SUBMITTER: Aalim Weljie Faith Coldren

PROVIDER: MTBLS27 | MetaboLights | 2016-12-15

REPOSITORIES: MetaboLights

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