| Project Overview: | Experiments conducted using yeast model systems have shown that polyploid yeast are dependent for survival upon increased expression of genes involved in pathways such as sister chromatid cohesion and mitotic spindle function. Furthermore, strains of aneuploid yeast show delayed cell cycle transition, an increase in glucose uptake, and a gene expression pattern characteristic of the environmental stress response. These experiments suggest that there are specialised adaptations required to sustain aneuploidy or polyploidy.We reasoned that mammalian CIN cancer cells might have acquired adaptations to tolerate a polyploid or aneuploid state similar to that in yeast and that these adaptations may be exploited and targetable to limit the survival of CIN cells specifically. Such a model is compelling since the therapeutic targeting CIN tumour cells may also reduce side effects associated with treatment by limiting cytotoxicity to normal diploid cells. To this end, we used a functional genomics approach to identifying regulators of CIN survival in human cancer, by performing unbiased whole genome RNAi screen in HCT116 (diploid) cell line and an isogenic MAD2 /- cell line. MAD2 heterozygosity is sufficient to induce CIN in this isogenic line. This approach might enable us to identify pathways that are necessary for survival of CIN cells, lead to potential new cancer drug targets and provide insight into the mechanisms sustaining CIN. |
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| Screener: | Alvin Lee (Swanton Lab). Extension:3462, Rm 115 |
| Project Status: | Published |
| Publications: | Ccdc13 is a novel human centriolar satellite protein required for ciliogenesis and genome stability.. Staples et al., 2014 |
| Project Start Date: | Mar 2009 |
| Keywords: | CIN MAD2 |
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