title: eIF4E promotes tumorigenesis and modulates chemosensitivity to cisplatin in esophageal squamous cell carcinoma.
abstract: Patients with esophageal squamous cell cancer are often diagnosed with advanced diseases that respond poorly to chemotherapy. Overexpression of eIF4E leads to enhance the translation of key malignancy-related proteins and enabling tumor growth and chemoresistance in a variety of human malignancies, but whether it has a role in ESCC remains obscure. We hypothesized that eIF4E promoted ESCC tumorigenesis and facilitated the development of acquired resistance to the cisplatin-based chemotherapy. In this study, we showed that eIF4E expression was increased significantly in clinical ESCC tissues and and ESCC cell lines and its expression level was correlated with lymph node metastasis, TNM stage, as well as overall and disease-free survival of ESCC. We also showed here that knockdown of eIF4E in EC9706 would dramatically reduced cell proliferation, colony formation, migration and invasion, apoptosis in vitro as well as in vivo, and vice versa. Moreover, "weak mRNAs" were demonstrated to be regulated by eIF4E in ESCC, which might interpret the above function. Overexpression of eIF4E decreased the efficacy of cisplatin-induced cell growth inhibition in ESCC cell line and xenograft model (P < 0.05). eIF4E knockdown by shRNA increased cisplatin-induced cytotoxicity in ESCC cell lines, and enhanced chemosensitivity to cisplatin in xenograft tumor models. Furthermore, we found that the PI3K/AKT pathway and Bcl-2/Bax ratio might be responsible for the eIF4E-induced cisplatin resistance in ESCC. Our data collectively show association of eIF4E expression with chemotherapeutic response in ESCC, and suggest that therapeutically targeting eIF4E may be a viable means of improving chemotherapy response in ESCC.
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Ting
authors: T
authors: Liu
authors: Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China.|Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Rong
authors: R
authors: Li
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Hui
authors: H
authors: Zhao
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Juan
authors: J
authors: Deng
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Ying
authors: Y
authors: Long
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Meng-Ting
authors: MT
authors: Shuai
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Qian
authors: Q
authors: Li
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Huan
authors: H
authors: Gu
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Ya-Qi
authors: YQ
authors: Chen
authors: Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors: Ai-Min
authors: AM
authors: Leng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D063646:Carcinogenesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D039561:Eukaryotic Initiation Factor-4E; D002945:Cisplatin
keywords: PI3K/AKT pathway; chemosensitivity; cisplatin; eIF4E; esophageal squamous cell carcinoma