Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/77722
Title: ELUCIDATING TUMOR SUPPRESSIVE FUNCTION OF FRATAXIN IN COLORECTAL CANCER WITH A QUANTITATIVE PROTEOMICS APPROACH
Authors: TAN XING FEI
Keywords: Proteomics, Cancer metabolism, Frataxin, iTRAQ, Warburg effect, HIF1α
Issue Date: 23-Jan-2014
Source: TAN XING FEI (2014-01-23). ELUCIDATING TUMOR SUPPRESSIVE FUNCTION OF FRATAXIN IN COLORECTAL CANCER WITH A QUANTITATIVE PROTEOMICS APPROACH. ScholarBank@NUS Repository.
Abstract: Metabolic alterations are essential for cancer cells to maintain their aggressive and proliferative behavior. Deficiency in Frataxin (FXN) was found to be associated with reduced mitochondrial ATP production and increased tumor progression. However, the molecular mechanisms behind FXN are largely unknown. To elucidate its role in tumor cells, we investigated the proteome changes induced by stable over-expression of FXN in colorectal cancer cell line HCT116 (OF). Using iTRAQ analysis, abundance of 276 proteins was found to be significantly different. Among them, EMMPRIN, a protein involved in tumor progression and malignancy, has a lower abundance in OF cells. Pathway analysis of these dysregulated targets recapitulated perturbed mitochondrial ATP production, (cellular reactive oxygen species (ROS) status and cell cycle and proliferation. Functional assays were performed to validate the effect of FXN over-expression. We then demonstrated that destabilization of HIF1a in OF cells could lead to associated metabolic changes and anti-cancer effect observed.
URI: http://scholarbank.nus.edu.sg/handle/10635/77722
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