Another HIF-independent angiogenesis pathway has been observed in HIF-1-deficient colon cancer cells, where increased production of ROS under hypoxia activates nuclear factor kappa B (NF-κB), which strongly induces angiogenic factors such as interleukin 8 (IL-8) [15,17] (Fig 7). The gene discussed is HIF1A; the disease is malignant colon neoplasm.