In addition, Staller and colleagues coulddemonstrate that CXCR4 is a hypoxiainducible gene with a HIF-1α binding domain, and that its overexpressionin clear-cell renal cell carcinoma is due to a loss-of-function of the vonHippel-Lindau (VHL) tumor suppressorprotein, which under normoxic conditions directs HIF-1α to ubiquitin-mediated degradation [35]. This evidence concerns the gene VHL and clear cell renal carcinoma.