摘要：SummaryTumor acquired radioresistance remains as the major limit in cancer radiotherapy (RT). Rab25, a receptor recycling protein, has been reported to be enhanced in tumors with aggressive phenotype and chemotherapy resistance. In this study, elevated Rab25 expression was identified in an array of radioresistant human cancer cell lines,in vivoradioresistant xenograft tumors. Clinical investigation confirmed that Rab25 expression was also associated with a worse prognosis in patients with lung adenocarcinoma (LUAD) and nasopharyngeal carcinoma (NPC). Enhanced activities of EGFR were observed in both NPC and LUAD radioresistant cells. Rab25 interacts with EGFR to enhance EGFR recycling to cell surface and to decrease degradation in cytoplasm. Inhibition of Rab25 showed synergized radiosensitivity with reduced aggressive phenotype. This study provides the clinical and experimental evidence that Rab25 is a potential therapeutic target to alleviate the hyperactive EGFR signaling and to prevent RT-acquired tumor resistance in patients with LUAD and NPC.Graphical AbstractDisplay OmittedHighlights•High expression of Rab25 is linked to radioresistance and EMT in lung cancer and NPC•Rab25 promotes cell therapeutic resistance via RTK-mediated signaling pathways•Rab25 elevates EGFR recycling rate onto the membrane in therapeutic-resistant cells•Targeting Rab25 combined with IR might be a potent treatment for the patients with cancerRadiation Biology; Molecular Biology; Cell Biology; Cancer
