Cell death & disease · 2017
EIF3D promotes gallbladder cancer development by stabilizing GRK2 kinase and activating PI3K-AKT signaling pathway.
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Zhang Fei, Xiang Shanshan, Cao Yang, Li Maolan, Ma Qiang, Liang Haibin, Li Huaifeng, Ye Yuanyuan, Zhang Yijian, Jiang Lin, Hu Yunping, Zhou Jian, Wang Xuefeng, Zhang Yong, Nie Lei, Liang Xiao, Gong Wei, Liu Yingbin
Аннотация
Recent evidence suggests that dysregulated eIF3d expression may be critical in various genetic disorders as well as cancer. In this study, we observed that EIF3d levels increased in gallbladder cancer (GBC) samples compared with non-tumor tissue. High eIF3d levels were associated with advanced tumor stage and metastasis and were correlated with poor prognosis in 92 patients with GBC. Depletion of EIF3d in GBC cell lines inhibited cell proliferation, colony formation and metastasis and induced apoptosis and cell cycle arrest in vitro and in vivo. In contrast, ectopic expression of eIF3d had the opposite effects. Moreover, in this study, we revealed that a novel non-translational factor function of eIF3d mediated its protumoral effects. In details, eIF3d stabilizes GRK2 protein by blocking ubiquitin-mediated degradation, consequently activates PI3K/Akt signaling, and promotes GBC cell proliferation and migration. In conclusion, eIF3d promotes GBC progression mainly via eIF3d-GRK2-AKT axis and it may be used as a prognostic factor. The therapeutic targeting of eIF3d-GRK2 axis may be a potential treatment approach for GBC.