Under severe hypoxia (<1% O2), NF-kB is activated by HIF-1α to enhance the invasive nature of tumor cells at the rim of GBM, whereas c-MYC is upregulated by HIF-2α under moderate hypoxia (2.5–5% O2) to promote the proliferation of tumor cells in GBM [164]. This evidence concerns the gene EPAS1 and neoplasm.