Metastasis is when cancer cells move from the original tumour to other sites in the body. It is a major cause of death in colorectal cancer patients. The identification of changes which occur within the cell during the progression of colorectal carcinoma is crucial in understanding this process. L-plastin is normally only expressed in white blood cells but is induced in 68% of carcinomas. We have demonstrated a link between L-plastin expression and colon cancer metastasis.

The aim of this project is to investigate the role of L-plastin in the development of metastasis using a cell line model of colonic epithelium. L-plastin will be expressed in this cell line, and its effect on parameters associated with metastasis, such as cellular movement, growth rates, and the ability of cells to invade into tissue will be analysed.

The effect of L-plastin over-expression on the tumour suppressor gene E-cadherin, a molecule which ‘sticks’ normal epithelial cells together, preventing detachment and metastasis, will also be measured. We will also mutate the L-plastin molecule to mimic its activated form and investigate the effect of mutated forms on colon cancer cells. These experiments will help elucidate the role of L-plastin in transformed cells, and will further current knowledge of mechanisms of cancer progression. L-plastin is already of use as a clinical marker of metastatic potential, and in the future may be the target of anti-metastatic therapies.