EGF and cancer: In addition to HIF-1α regulation by the EGF/EGFR transduction pathway in a hypoxia-independent manner, HIF proteins can regulate their own production through autocrine and additive loops by which hypoxia induces EGF/EGFR expression while the ensuing EGFR signaling synergizes with hypoxia to induce HIF-1α and/or HIF-2α to promote cancer cell survival, migration, and invasion [199,200,204,205,206].