Cell adhesion and signaling in oncogenesis

The main objective of my research is to understand the molecular basis of how cancer progresses and to use the knowledge to identify new cancer therapies. To achieve this, my research team is studying receptors found on the surface of most cells that cause them to attach to other cells. We want to determine how the receptors communicate information they detect on the outside of the cell to the inside of the cell. We have identified proteins that interact with these receptors on the inside of the cell and are responsible for transmitting information to other parts of the cell to control cell division, cell death, cell differentiation and cell movement. We are focusing on one protein - Integrin Linked Kinase (ILK) - whose function is tightly regulated in normal cells, where its activity rapidly turns on and off. But in cancer cells, ILK is on all the time, leading to increased cell division, decreased cell death and increased cell movement. We have determined that ILK is at least partly responsible for the abnormal behaviour of cancer cells, and ILK activity is considerably elevated in many types of cancer. We have also identified specific chemical inhibitors of ILK activity, which are currently being evaluated in pre-clinical trials. The results to date show these inhibitors are effective in blocking growth and spread of tumours. ILK is present in many tissue types, and it is likely that it plays a critical role in the development and function of these tissues, and in other diseases of chronic inflammation such as arthritis, asthma, kidney disease and heart disease. To investigate this further we are using genetic techniques to alter ILK expression and function in a tissue-specific manner. Such studies will lead to a better understanding of the role of ILK and related proteins in nomal and diseased tissues.