Taken together this may indicate either a transcriptional downregulation of the receptor induced by EGF or the presence of a negative regulatory feedback loop, activated upon excessive EGF binding, which may result in endocytosis and degradation of EGF-EGFR complexes.24 Although in cancer this loop may be normally bypassed in order to provide continuous oncogenic signaling, the chronic stimulation by EGF in stem cell media might result in an overstimulation of receptor activity, triggering its degradation. Here, EGF is linked to cancer.