Grant: Project Grant

Building the cell's protein factories is a complex job involving many hundreds of components and takes up much of a cell's efforts to grow. For cancers to grow, they must find ways to make more of these protein factories than surrounding normal tissues. So, if we could find ways to limit the manufacture the protein factories, known as ribosomes, we could control cancer. In fact, we have recently demonstrated that targeting the genes that make the RNAs of the ribosome kills cancer cells while leaving normal cells untouched. Several "tumour suppressor" proteins prevent cancer by doing just this. For example, the ARF and TP53 tumour suppressors are very important in limiting ribosome production and either or both are inactivated in 80% of cancers. We recently discovered that highly proliferative cancer cells show an unusual "epigenetic silencing" of the Ribosomal RNA genes. Epigenetic silencing is one means by which genes are selectively inactivated to establish different tissues such as skin, bone, blood, intestine, etc. We found that silencing of the Ribosomal RNA genes is lost in some cancer cells and closely resembles the situation in the embryonic stem cells that will create all the different tissues of the body. We discovered some years ago that the ARF tumour suppressor regulates a protein called TTF1. This protein is known to determine epigenetic silencing of the Ribosomal RNA genes. We hypothesize that the changes in ribosomal RNA gene silencing may allow pre-cancerous cells to grow rapidly, but more importantly cause the type of chromosome rearrangements that lead to full-blown cancer. Our lab. is trying to understand how this happens in the hope of discovering novel and more effective ways of treating cancer.