Eukaryotic translation initiation factor 3B accelerates the progression of esophageal squamous cell carcinoma by activating β-catenin signaling pathway.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors. Eukaryotic translation initiation factors 3B (EIF3B) is considered to influence tumor proliferation, invasion, apoptosis and cell cycle, which act together to promote the progression of tumors. However, the role of EIF3B in ESCC is unknown. This study aims to explore the clinical and biological role of EIF3B in ESCC.


RESULTS
EIF3B expressions were up-regulated in both ESCC tissues and cell lines. Overexpression of EIF3B was associated with tumor depth, lymph node metastasis and advanced TNM stage. Importantly, patients with high EIF3B expression suffered shorter overall and disease-free survival. Knockdown of EIF3B could inhibit cell proliferation and invasion, promote cell apoptosis, and interfere the cell cycle in vitro. EIF3B-knockdown cells could form smaller subcutaneous tumors in vivo. Finally, we demonstrated EIF3B could activate β-catenin signaling pathway.


METHODS
Immunohistochemical staining and Western blot were performed to detect the EIF3B expression in ESCC patient tissues and cell lines. The association between EIF3B expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Then, CCK-8, colony-formation, Transwell and wound-healing assay were performed to compare the bio-functional change after knockdown of EIF3B. Flow cytometry was applied to analyze the change of cell apoptosis and cycle induced by EIF3B knockdown. Tumor xenograft assay was done to verify the in-vitro results.


CONCLUSIONS
EIF3B might serve as a novel marker for predicting prognosis of ESCC patients and as a potential therapeutic target, individually or together with other subunits of EIF3 complex.
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Fengkai
F
Xu
Department of Otolaryngology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Cheng-Zhi
CZ
Xu
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Jie
J
Gu
Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, P. R. China.
Xiaoming
X
Liu
Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, P. R. China.
Ronghua
R
Liu
Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, P. R. China.
Enyu
E
Huang
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Yunfeng
Y
Yuan
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Guangyin
G
Zhao
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Jiahao
J
Jiang
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Chen
C
Xu
Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, P. R. China.
Yiwei
Y
Chu
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Chunlai
C
Lu
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Di
D
Ge
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C000589329:EIF3B protein, human; D039621:Eukaryotic Initiation Factor-3; D034741:RNA, Small Interfering; D051176:beta Catenin
esophageal squamous cell carcinoma; eukaryotic translation initiation factors 3B; β-catenin signaling pathway