title: eIF3i activity is critical for endothelial cells in tumor induced angiogenesis through regulating VEGFR and ERK translation.
abstract: Translational control is a critical step in the regulation of gene expression. Accumulating evidence shows that translational control of a subgroup of mRNAs tends to be selective. However, our understanding of the function of selective translational control in endothelial cells is still incomplete. We found that a key translational regulator, eIF3i, is highly expressed in endothelial cells during embryonic and tumor angiogenesis. Knockdown of eIF3i restrained cell proliferation and migration in endothelial cells. In zebrafish angiogenesis model, eIF3i mutant endothelial cells could not respond to induction signals from tumor mass. Mechanistically, we showed that eIF3i knockdown reduced VEGFR/ERK signaling by down-regulating VEGFR2 and ERK protein expression. Gene therapy model suggested that the growth and metastasis of cancer cells were suppressed by eIF3i shRNA. Therefore, our work established a selective translational regulatory mechanism during tumor induced angiogenesis and suggested that targeting eIF3i may be applicable for anticancer therapy.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yao
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D014176:Protein Biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D039621:Eukaryotic Initiation Factor-3; C096013:EIF3I protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: ERK; VEGFR; eIF3i; selective translational control; tumor angiogenesis