Journal article
EIF3D promotes gallbladder cancer development by stabilizing GRK2 kinase and activating PI3K-AKT signaling pathway
Cell death & disease, v 8(6), pp e2868-e2868
01 Jun 2017
PMID: 28594409
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- EIF3D promotes gallbladder cancer development by stabilizing GRK2 kinase and activating PI3K-AKT signaling pathway
- Creators
- Fei Zhang - XinHua HospitalShanshan Xiang - XinHua HospitalYang Cao - XinHua HospitalMaolan Li - XinHua HospitalQiang Ma - XinHua HospitalHaibin Liang - XinHua HospitalHuaifeng Li - XinHua HospitalYuanyuan Ye - XinHua HospitalYijian Zhang - XinHua HospitalLin Jiang - XinHua HospitalYunping Hu - XinHua HospitalJian Zhou - XinHua HospitalXuefeng Wang - XinHua HospitalYong Zhang - XinHua HospitalLei Nie - The University of Texas MD Anderson Cancer CenterXiao Liang - Sir Run Run Shaw HospitalWei Gong - XinHua HospitalYingbin Liu - XinHua HospitalHualou Liang - School of Biomedical Engineering, Science, and Health Systems (1997-)
- Publication Details
- Cell death & disease, v 8(6), pp e2868-e2868
- Publisher
- Springer Nature
- Number of pages
- 12
- Grant note
- 13XJ10037 / Natural Science Research Foundation of Shanghai Jiao Tong University School of Medicine 15QA1403100 / Shanghai Rising-Star Program 14JCRY05 / Interdisciplinary Program of Shanghai Jiao Tong University 2012AA022606 / National High Technology Research and Development Program (863 Program); National High Technology Research and Development Program of China 12410705900 / Shanghai Science and Technology Commission Intergovernmental International Cooperation Project 2015 M571577 / China Postdoctoral Science Foundation Program for Changjiang Scholars; Program for Changjiang Scholars & Innovative Research Team in University (PCSIRT) YG2011ZD07 / Foundation for Interdisciplinary Research of Shanghai Jiao Tong University 81172026; 81272402; 81301816; 81172029; 91440203; 81402403; 81672404; 81502433 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) 20130073130014 / Leading Talent program of Shanghai and Specialized Research Foundation for the PhD Program of Higher Education-Priority Development Field 12401905800 / Shanghai Science and Technology Commission Medical Guiding Project
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000405895200046
- Scopus ID
- 2-s2.0-85041119140
- Other Identifier
- 991019320713304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology