Project 171800

Transforming growth factor-beta (TGFß) is a cytokine that normally acts as a tumor suppressor. However, in lung tumors it switches roles and aides tumor cells to become metastatic. We will investigate the regulation of this switch and how TGFß signals are regulated in lung cell tumors. TGFß associates with cell surface receptors, which internalize rapidly into the cell body. The interaction of these activated receptors with different molecules in their cellular travels will affect signaling outcome. In this study we propose to analyze a novel aspect of TGFß regulation; the relationship between TGFß receptor traffic and signal transduction. We propose to analyze how proteins that associate with the receptors alter TGFß receptor trafficking and signaling. These proteins will then be tested for their TGFß-dependent metastatic potential of lung cancer cells. This will be tested by analyzing lung cancer cell growth, migration and invasion in cell culture models. This research will identify molecules that will be eventually used as therapeutic targets in lung cancer patients.