NOS3 and cancer: In summary, the most significant and novel findings presented in this study include that 1) ephrin-A1 cooperates with eNOS in promoting angiogenesis in HUVECs; that 2) cross-talk between ephrin-A1 and eNOS is mediated by PI3K/Akt-dependent pathway; and that 3) hypoxia up-regulates both membrane-bound and secreted ephrin-A1 protein in cancer cells.