Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, Changsha 410008, China; Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
Bowen Xie
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, Changsha 410008, China; Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
Yanfang Qiu
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
Di Jing
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
Jing Zhang
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
Yumei Duan
Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China
Zhi Li
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, Changsha 410008, China
Ming Fan
Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
Jiang He
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, Changsha 410008, China
Yuanzheng Qiu
Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
Rong Tan
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, Changsha 410008, China
Jian Jian Li
Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA; NCI-desginaged Comprehensive Cancer Center, Sacramento, CA 95817, USA; Corresponding author
Lun-Quan Sun
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders Xiangya Hospital, Changsha, China 410008; Corresponding author
Summary: Tumor 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 vivo radioresistant 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. : Radiation Biology; Molecular Biology; Cell Biology; Cancer Subject Areas: Radiation Biology, Molecular Biology, Cell Biology, Cancer
