Wnt proteins are important secreted signaling molecules which regulate numerous biological processes, including tissue development, cell proliferation and tumorigenesis. Many Wnt proteins, such as Wnt1, signal through the canonical Wnt/beta-catenin pathway which leads to beta-catenin stabilization. Other Wnt proteins, like Wnt5a, signal through alternative non-canonical pathways which are beta-catenin independent. Wnt5a has been reported to be upregulated in several types of human malignancies, including breast cancer. There are inconsistent lines of evidence suggesting that Wnt5a can either promote or antagonize tumor progression in other tissues. Given the frequent overexpression of Wnt5a in breast cancer and the conflicting data regarding the suggested function of Wnt5a, the goal of this proposal is to directly determine whether Wnt5a acts as an oncogene or a tumor suppressor in the mammary gland. In addition, we will elucidate molecular mechanisms of Wnt5a signal transduction in mammary cells. These studies will enhance our understanding of Wnt5a signaling in mammary cancer and provide insights into the design of diagnostic and therapeutic approaches applicable to human breast cancer. ? ? ?
