EGLN3 and osteosarcoma: For instance, in U2OS (human osteosarcoma) cells, the accumulation of the PHD2 and PHD3 proteins by hypoxia led to accelerated HIF-1 degradation after reoxygenation, while HIF-1 translation in RKO (human colon carcinoma) cells was inhibited by a decrease in GSK3β under prolonged hypoxia [22, 23].