The tumorigenesis of breast cancer is a complex process involving multiple factors, among which abnormal gene expression is a key event. Nevertheless, studies on the regulation of gene expression have focused primarily on the transcriptional level, although the abnormal translation regulation is also closely related to tumorigenesis. Accumulating evidence has indicated the dysregulation of eukaryotic initiation factor (eIF) subunits in a variety of tumors, which contributes to the malignant transformation, tumor growth, metastasis, and the prognosis of patients. In this study, we examined the expression of eIF3b and found an upregulation of eIF3b in breast cancer cell lines as well as tumor tissues. In addition, the expression of eIF3b was related to the tumor stage with highest eIF3b expression in TNM stage III-IV and/or lymph node metastatic breast cancer. Furthermore, in vitro experiments demonstrated that eIF3b knockdown markedly inhibited tumor hyperplasia as well as the migration and invasion of breast cancer cells, while eIF3b overexpression showed the opposite effects. Importantly, eIF3b silencing inhibited the growth and pulmonary metastasis of xenograft tumor in breast cancer mouse model. Mechanistically, we found that eIF3b downregulation suppressed the malignant development of breast cancer by modulating Wnt/β-catenin pathway. Collectively, our data suggested that eIF3b might not only participate in the tumorigenesis of breast cancer, but also promote the proliferation, invasion, and metastasis of tumor cells. Thus, eIF3b may service as a potential therapeutic target for the treatment of patients with breast cancer.
Keywords: Breast cancer; Wnt/β-catenin pathway; eukaryotic initiation factor 3B; invasion; metastasis; tumor growth.
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