The GPI-linked cell surface glycoprotein, CD24, has been shown to be a biomarker of and contributor to carcinogenesis and metastasis in several tumor types. The transcription factor, HIF-1α, plays a key role in physiologic and neoplastic hypoxia, regulating expression of several oncogenic transcriptional targets. Herein, Thomas and colleagues provide a mechanistic link between these two key proteins in cancer biology by showing that HIF-1α directly regulates CD24 at its promoter and that the prometastatic activity of HIF-1α in experimental metastasis models of bladder and prostate cancer depends on CD24 expression. Immunohistochemical studies using human bladder cancer tissues (pictured on cover) found that expression of HIF-1α and CD24 was correlated, whereas simultaneous low expression of these biomarkers was associated with the best overall patient survival, supporting the clinical relevance of this pathway. For details, see article by Thomas and colleagues on page 5600.