Taken together, CXCL12/CXCR4 signaling has a dual impact in bone metastasis: newly arrived cancer cells in bone use CXCL12/CXCR4 and integrin interactions to localize to the endosteal niche, and established bone tumors use CXCL12/CXCR4 transactivated growth factor receptor signaling for expansion of bone tumors. The gene discussed is CXCL12; the disease is cancer.