Cancer biology and PTEN: what exactly goes wrong?

All cells use a variety of biochemical mechanisms to control their behaviour in response to changes in their environment, whether they are single cells or those making up a large complex organism. Our laboratory studies one important biochemical pathway in this signal transduction process, one which is very frequently mis-controlled in human disease. The PI 3-kinase/PTEN signalling pathway is a key regulator of the growth, survival and motility of many cell types and its uncontrolled activity is a characteristic of most tumours and many other diseases. Our work aims to understand in more detail the workings of the proteins that make up the core of this pathway, and the lipid signalling molecules that they synthesise and metabolise. We are using a variety of approaches from enzymology, proteomics and lipid biochemistry to functional studies in cultured cells and in vivo. Our current work reveals novel insight into the function of the PTEN tumour suppressor. It also implies that many tumours are driven by changes downstream of PTEN/PI3K other than the canonical pathways involving the heavily-studied AKT kinases that have been the focus of intense cancer drug discovery efforts.