The Wnt pathway is one of the major mechanisms that allow cells to respond to specific signals to change their genetic program and to proliferate.  In the adult, this pathway is generally shut off. It can happen, however, that it is accidentally re-activated, either by some mutations, or by some other and still not always well understood ways. This re-activation is extremely dangerous, as cells can start now proliferate in an uncontrolled manner, become cancerous, and form tumors.
Despite the huge effort to study this pathway, several important aspects remain obscure. The study is complicated by the fact that the components of the pathway can be located in different parts of the cells, performing different functions, and it has been so far difficult to separate these pools and distinguish their activities. We have now established a new method that can very cleanly and efficiently separate from each other the main compartments and study them in isolation.  We will use this technique to study in detail the properties of β-catenin, the molecule that travels from the cell surface to the interior of the nucleus to transmit the signal to DNA. We suspect that it is modified at the surface by a specific activation event that makes it particularly effective at reaching its target.
This project will study a very important aspect of the Wnt pathway. Identification of specific modifications of β-catenin would have a real impact on future searches for drugs that would block its uncontrolled activation in cancer cells.