title: XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma.
abstract: Radiotherapy is widely applied for treatment of esophageal squamous cell carcinoma (ESCC). The Rad51-related protein XRCC3 plays roles in the recombinational repair of DNA double-strand breaks to maintain chromosome stability and repair DNA damage. The present study aimed to investigate the effect of XRCC3 on the radiotherapy response of ESCC and the underlying mechanisms of the roles of XRCC3 in ESCC radiosensitivity. XRCC3 expression in ESCC cells and tissues was higher than that in normal esophageal epithelial cells and corresponding adjacent noncancerous esophageal tissue. High XRCC3 expression was positively correlated with resistance to chemoradiotherapy in ESCC and an independent predictor for short disease-specific survival of ESCC patients. Furthermore, the therapeutic efficacy of radiotherapy in vitro and in vivo was substantially increased by knockdown of XRCC3 in ESCC cells. Ectopic overexpression of XRCC3 in both XRCC3-silenced ESCC cells dramatically enhanced ESCC cells' resistance to radiotherapy. Moreover, radiation resistance conferred by XRCC3 was attributed to enhancement of homologous recombination, maintenance of telomere stability, and a reduction of ESCC cell death by radiation-induced apoptosis and mitotic catastrophe. Our data suggest that XRCC3 protects ESCC cells from ionizing radiation-induced death by promoting DNA damage repair and/or enhancing telomere stability. XRCC3 may be a novel radiosensitivity predictor and promising therapeutic target for ESCC.
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Weiran
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Xianliang
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Lung Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Minghan
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Maobin
authors.initials: M
authors.lastname: Meng
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Hongqing
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Lujun
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Pang
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Qian
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D011836:Radiation Tolerance / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3
keywords: Esophageal squamous cell carcinoma; XRCC3; homologous recombination; radiotherapy; telomere stability