The role of the Par6-PI3K signaling axis in TGFbeta tumour suppressor in breast cancer metastasis Metastasis, the dissemination of a tumour to distant sites, causes 90% of deaths by breast cancer. This is due to the inability of metastatic cancer cells to die and stop their activity in response to current treatments. Transforming growth factor beta (TGFbeta) is a protein produced by breast tumours which promote metastasis, but can paradoxically inhibit tumour growth in the early stages of breast cancer development, due in part to its capacity to promote cell death. Knowing how the cancer cell transduces the signal provided by TGFbeta into a cue that trigger its own destruction is important for our understanding of breast cancer biology and might lead to the discovery of more effective ways to kill cancer cells. We have identified two proteins: Par6 and PI3K, which we believe are essential components of a machinery that dictates a cell's decision to live or die in response to TGFbeta. This research aims to demonstrate that these proteins interact and this is important to trigger TGFbeta-dependent cell death. We also propose to manipulate these proteins in TGFbeta-dependent metastatic breast cancer cells to demonstrate we can “force” these cells to die in response to this growth factor, thus discovering new venues to treat metastatic breast cancer. The final outcome of this research will help discovering new chemotherapeutic agents for TGFbeta-dependent metastatic breast cancer or some other agents that make these tumours more susceptible to the current chemotherapeutic options.