Grant: Project Grant

Building the cell's protein factories, the ribosomes, is a complex task that involves many hundreds of components and absorbs much of a cell's efforts to grow. This is especially in cancer where tumour cells find ways to increase ribosome production in order to grow and out-compete surrounding normal tissues. If we could find ways to limit ribosome production, we would be able to control a broad range of cancers. Though this sounds simplistic, we have recently demonstrated in model systems that targeting the genes coding for the large RNAs that make up the ribosome kills cancer cells while leaving normal cells untouched. In fact, many already used chemo-drugs do exactly this, though this fact has largely been ignored in favour of more complex theories. However, novel chemo-drugs specifically designed to limit ribosome manufacture are now being developed and tested. We and others have also shown that several "tumour suppressors" also naturally prevent cancer by suppressing ribosome manufacture. 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. These activities have in the main part been overlooked in the rush to identify so-called cancer- causing genes, all of which logically must increasing ribosome production either directly or indirectly. Unfortunately, the key genes coding the RNAs of the ribosome are "for convenience" omitted from all bioinformatic searches for the genetic signatures of cancer. Our studies over the last years have attempted correct this by directly studying the links between cancer and ribosome production. We propose to continue to develop this work by delving into the mechanisms controlling ribosome production in a range of important cancers including Breast, Liver and Colorectal Cancers, as well as the actions of Tumour Suppression and of novel Drugs.