As a pro-metastatic factor for many of these cancers, RANKL/RANK signaling promotes primary tumor cell proliferation, invasion, migration, and colonization by influencing a wide spectrum of cellular properties from driving the epithelial-mesenchymal transition (EMT) program [18, 20, 21], expanding the cancer stem cell population [18, 22], attracting infiltrating tumor associated macrophages to the tumor microenvironment [23, 24], to facilitating metastatic colonization of circulating tumor cells to distant anatomic sites such as bone and lung [11, 12, 14, 17, 18, 23–25]. This evidence concerns the gene TNFSF11 and cancer.