TY - JOUR
T1 - Eif3d promotes gallbladder cancer development by stabilizing grk2 kinase and activating pi3k-akt signaling pathway
AU - Zhang, Fei
AU - Xiang, Shanshan
AU - Cao, Yang
AU - Li, Maolan
AU - Ma, Qiang
AU - Liang, Haibin
AU - Li, Huaifeng
AU - Ye, Yuanyuan
AU - Zhang, Yijian
AU - Jiang, Lin
AU - Hu, Yunping
AU - Zhou, Jian
AU - Wang, Xuefeng
AU - Zhang, Yong
AU - Nie, Lei
AU - Liang, Xiao
AU - Gong, Wei
AU - Liu, Yingbin
N1 - Funding Information:
Acknowledgements. This study was supported by the National Natural Science Foundation of China (nos. 81172026, 81272402, 81301816, 81172029, 91440203 and 81402403, 81672404 and 81502433), the National High Technology Research and Development Program (863 Program, no. 2012AA022606), the Foundation for Interdisciplinary Research of Shanghai Jiao Tong University (no. YG2011ZD07), the Shanghai Science and Technology Commission Intergovernmental International Cooperation Project (no. 12410705900), the Shanghai Science and Technology Commission Medical Guiding Project (no. 12401905800), the Program for Changjiang Scholars, the Natural Science Research Foundation of Shanghai Jiao Tong University School of Medicine (no. 13XJ10037), the Leading Talent program of Shanghai and Specialized Research Foundation for the PhD Program of Higher Education-Priority Development Field (no. 20130073130014), the Interdisciplinary Program of Shanghai Jiao Tong University (no. 14JCRY05), the Shanghai Rising-Star Program (no. 15QA1403100) and the China Postdoctoral Science Foundation (no. 2015 M571577).
Publisher Copyright:
© The Author(s) 2017.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.1038/cddis.2017.263
DO - 10.1038/cddis.2017.263
M3 - Article
C2 - 28594409
AN - SCOPUS:85041119140
SN - 2041-4889
VL - 8
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 6
M1 - e2868
ER -