Ras oncogene as a mediator of three-dimensional tumour growth

Project summary: The cells lining many human organs (epithelial cells) form a single layer, and any cells that become detached from this layer stop growing. Most tumours are composed of those epithelial cells that have become cancerous and which now have to grow outside of the epithelial layer in order to be able to spread throughout the body. We are investigating the mechanisms allowing detached cancer cells to grow outside of their original location. Previous research: A cellular protein called Ras is normally activated by signals coming from outside of the cell and can, in turn, trigger events that change cellular levels of many proteins. Genetic alterations in cancer cells can make Ras active at all times and this contributes to the progression of many cancers. One of the properties of Ras that is thought to make it a major factor in cancer is its ability to promote growth of tumour cells outside of the original epithelial layer. Ras exerts this effect via several mechanisms. Dr Rosen and his colleagues have begun to identify them but knowledge about these mechanisms is far from complete. Project description: Dr Rosen?s group found recently that Ras promotes growth of cancer cells outside of their original location by triggering the reduction in the levels of a cell growth inhibiting protein called Beclin 1 in these cells. The mechanisms by which Ras exerts this effect on Beclin 1 could serve as targets for a novel type of cancer therapy aimed at the suppression of cancer cell growth outside of the original epithelial layer and their spread throughout the body. Dr Rosen has begun to study these mechanisms but they remain largely unknown. The goal of this study is to understand them. Impact and relevance: As a result of thesestudies, Dr Rosen expects to understand the mechanisms allowing cancer cells to grow outside of the epithelial layer. Suppression of these mechanisms can be anticipated to block the growth of these cells outside of their original location and thus stop or slow down the progression of the disease. If successful, this work could give rise to a new type of cancer therapy based on preventing the spread of cancer cells throughout the body.