| Project Overview: | As part of a collaborative effort a preliminary group of approximately sixty target genes have been identified using a systems biology approach – the first developed cancer cell metabolism model - and from the literature, that are involved in different aspects of lipid metabolism, for example, fatty acid biosynthesis, cholesterol biosynthesis and transcriptional regulators. We aim to validate and identify a number of these targets as being essential for the survival of breast and prostate cancer cells under normoxic and hypoxic conditions (20% and 0.1% O2, respectively) in differing serum concentrations (10% and1% FCS). To do this we will use a panel of cell lines from a range of genetic backgrounds and perform a validation screen. The most promising targets will be taken forward and their role in promoting cancer cell survival will be assessed using gene silencing in 2D and 3D in vitro cultures and in vivo xenographs. Moreover, we will characterise the role these targets play in cancer cell biology and how this could be exploited therapeutically, eitheralone or in combination with small molecule inhibitors that are known to target signalling pathways that are perturbed in cancer, such as the PI3K-AKT signalling cascade. Furthermore, we will examine candidate gene expression using proprietary and non-proprietary (e.g. oncomine) datasets to confirm their expression in human tumours, strengthening the importance of these genes inpromoting cancer progression and survival. The project also has the wider remit of furthering our knowledge of the role lipid metabolism plays in cell biology, providinginformation that will hopefully be of interest and importance to the scientific community. |
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| Screener: | Barrie Peck (Schulze Lab). Extension:2049, Rm 113 |
| Project Status: | Published |
| Publications: | Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress.. Schug et al., 2015 |
| Project Start Date: | March 2012 |
| Keywords: | Hypoxia Metabolism Normoxia Viability |
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