EBV-LMP1 suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma

Highlights • A new mechanism for EBV-encoded LMP1-mediated radioresistance is proposed. • The mechanism relies on the suppression of DDR by LMP1 through inhibiting the DNA-PK/AMPK signaling pathway. • LMP1 impaired DSB repair in NPC cells induced by irradiation, possibly by inhibiting DNA-PK phosphorylation and activity. • The AMPKα (Thr172) reduction was associated with a poorer clinical outcome of radiation therapy in NPC patients. • The reactivation of AMPK significantly promoted radiosensitivity both in vivo and in vitro , which could provide a mechanistic rationale supporting the use of AMPK activators, such as metformin, for enhancing NPC radiotherapy.