CXCR4 and neoplasm: HIF-1 activates the transcription of genes involved in key aspects of cancer biology, and regulates the expression of many downstream genes, including hypoxic energy metabolism (PDK1 and LDHA), angiogenesis (VEGF and EPO), intracellular matrix remodeling (MMP1 and LOX), apoptosis/autophagy (BNIP3 and NIX), cell survival (Myc and IGF family) and cell invasion/migration and escape (CXCR4), etc. All of these make tumor cells resistant to hypoxia, and increase oxygen/energy supply, thereby promoting tumor growth, invasion, and metastasis [71,72].