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- W100487651 abstract "Sterol regulatory element binding proteins (SREBPs) are transcription factors thatregulate the expression of genes involved in fatty acid and cholesterol biosynthesis. Ithas been established that SREBPs are regulated downstream of the PI3-Kinase/Akt/mTORC1 signalling axis, a pathway that is frequently hyper-activated in cancer.SREBP target genes are upregulated in some forms of human cancer and a role for lipidmetabolism in tumourigenesis has been suggested.Glioblastoma multiforme (GBM) is a cancer type that is associated with hyperactivationof the PI3-kinase/Akt signalling pathway and frequently displays poorly oxygenated(hypoxic) regions. SREBP1 has been implicated in the tumourigenic potential of thiscancer type. However, the exact role of SREBPs in tumourigenesis is not known. Inoder to investigate the SREBP-transcriptional response in cancer cells, a geneexpression microarry analysis was carried out. It was found that SREBPs regulate genesinvolved in a variety of cellular processes including lipid metabolism, cell cycleregulation, redox regulation and cellular stress response. In addition, the role ofSREBPs in lipid metabolism in hypoxia was investigated. It was found that hypoxialeads to distinct changes in the expression of different SREBP isoforms and their targetgenes and is associated with a decrease in pyruvate-dependent lipid synthesis andincreased lipid storage.SREBPs are regulated downstream of the Akt/mTORC1 pathway, although the exactmechanism of this regulation remains to be elucidated. Possible mechanisms by whichAkt and mTORC1 regulate SREBPs were investigated. It was found that inhibition ofmTORC1 differentially affects the expression of individual SREBP isoforms. Theresults described in this thesis also show that mTORC1 modulates the transcriptionalactivity of mature SREBP and may regulate its stability in a GSK3-independentmanner." @default.
- W100487651 created "2016-06-24" @default.
- W100487651 creator A5020220514 @default.
- W100487651 date "2012-02-28" @default.
- W100487651 modified "2023-09-26" @default.
- W100487651 title "Sterol regulatory element binding proteins: their role in the hypoxic response of cancer cells and their regulation by the Akt/mTORC1 pathway" @default.
- W100487651 hasPublicationYear "2012" @default.
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