Since our above studies demonstrated that hypoxia and the HIF-1α/VHL axis was critical in the regulation of CXCR4 expression and function in RCC cell lines, and our previous study identified the major organs that express elevated levels of CXCL12 (i.e., lungs, adrenal glands, bone marrow, liver, and brain, as compared to the primary tumors) [7]; we next wanted to determine whether alteration of VHL expression by knockdown could lead to changes in metastatic behavior of RCC. The gene discussed is VHL; the disease is renal cell carcinoma.