Figure 2.

Overview of potential mechanisms by which epidermal growth factor (EGFR) stimulates DNA double-strand break repair, leading to radioresistance. (A) Ionizing radiation (IR) stimulates membrane-bound EGFR, which may lead to translocation of the receptor to the nucleus. Ionizing radiation may induce the activation of EGFR directly in the nucleus. (B) Exogenous stimulation of EGFR by related ligands, such as EGF and transforming growth factor α (TGFα), as well as autocrine secretion of EGFR ligands, such as in tumor cells harboring the KRAS mutation, induce nuclear translocation of EGFR. Following irradiation, activated EGFR in the nucleus stimulates DNA repair machinery by stimulating the phosphorylation/activation of proteins involved in DNA damage response (DDR) and DSB repair. EGFR may also function as a transcription factor regulating proteins involved in DSB repair.