ZFIN ID: ZDB-PUB-170215-2
eIF3i activity is critical for endothelial cells in tumor induced angiogenesis through regulating VEGFR and ERK translation
Zhang, Y., Wang, P., Zhang, Q., Yao, X., Zhao, L., Liu, Y., Liu, X., Tao, R., Yu, C., Li, Y., Song, X., Yao, S.
Date: 2017
Source: Oncotarget   8(12): 19968-19979 (Journal)
Registered Authors: Li, Yuhao, Wang, Ping, Yao, Shaohua, Yu, Chuan, Zhang, Yaguang
Keywords: ERK, VEGFR, eIF3i, selective translational control, tumor angiogenesis
MeSH Terms:
  • Animals
  • Apoptosis
  • Biomarkers, Tumor/genetics
  • Biomarkers, Tumor/metabolism
  • Cell Movement
  • Cell Proliferation
  • Eukaryotic Initiation Factor-3/genetics
  • Eukaryotic Initiation Factor-3/metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Human Umbilical Vein Endothelial Cells/pathology*
  • Humans
  • Melanoma, Experimental/blood supply*
  • Melanoma, Experimental/metabolism
  • Melanoma, Experimental/pathology
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinase 1/genetics
  • Mitogen-Activated Protein Kinase 1/metabolism*
  • Mitogen-Activated Protein Kinase 3/genetics
  • Mitogen-Activated Protein Kinase 3/metabolism*
  • Neovascularization, Pathologic/metabolism
  • Neovascularization, Pathologic/pathology*
  • Protein Biosynthesis
  • Receptors, Vascular Endothelial Growth Factor/genetics
  • Receptors, Vascular Endothelial Growth Factor/metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed: 28193911 Full text @ Oncotarget
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.