Wnt signaling is suggested to be important in survival and invasion of myeloma cells. Our previous studies demonstrated that two Wnt signaling pathways are activated in response to Wnt3a. We believe that other Wnts, including Wnt3 and Wnt5a, also play an important role in myeloma survival and invasion. We will study the role of these Wnts to such processes. We will also study strategies to interfere with their signaling. These studies will not only benefit understanding the role of Wnts in the biology of myeloma, but more importantly will help form the basis for new therapeutic strategies.