- Title
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eIF3i activity is critical for endothelial cells in tumor induced angiogenesis through regulating VEGFR and ERK translation
- Authors
- Zhang, Y., Wang, P., Zhang, Q., Yao, X., Zhao, L., Liu, Y., Liu, X., Tao, R., Yu, C., Li, Y., Song, X., Yao, S.
- Source
- Full text @ Oncotarget
eIF3i is expressed in zebrafish and mammalian endothelial cells. A. eIF3i is expressed in endothelial cells of 24 hpf zebrafish embryos as determined by WISH. The black arrowheads point to the dorsal aorta and intersegment vessels of embryos. B. Human umbilical vein endothelial cells (HUVECs) expressed eIF3i. The red channel represents eIF3i, and the blue channel represents the cell nucleus. Scale bars, 10μm. C. eIF3i siRNAs significantly inhibited eIF3i protein level. GAPDH was used as a loading control. Fold changes are compared with mock and presented below each blot. D. eIF3i siRNAs significantly inhibited eIF3i mRNA level. (n=3).***p<0.001. E. HCM increased the expression of eIF3i in HUVECs. Tubulin was used as a loading control. Fold changes are compared with BM and presented below each blot. BM, basic medium; CM, B16 cell non-hypoxic conditional medium; HCM, B16 cell hypoxic conditional medium. EXPRESSION / LABELING:
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eIF3i acts an autonomous function in zebrafish vascular endothelial cells. A. Schematic diagram of zebrafish embryos cell transplantation. The donors were wildtype or eIF3i-/-; flk1:GFP transgenic zebrafish embryos. The recipients were wildtype flk1:mCherry zebrafish embryos. The green arrows point to the operation direction. B. Diagram showing the region of interest (ROI) that was used for quantification of angiogenesis. C. Representatives of host embryos receiving either wildtype or eIF3i-/- donor cells at 48 hpf. The white arrowheads point to intersegment vessels derived from donor cells. Scale bars, 500μm. D. Quantification of donor derived intersegment vessels. |
eIF3i is required for vascular endothelial cells to respond to tumor signals. A. Knockdown of eIF3i suppressed tumor induced HUVECs migration. BM, basic medium. HCM, hypoxic conditional medium. Scale bars, 100μm. B. The statistics of invaded cell. BM/control siRNA (n=4), BM/eIF3i siRNA 1# (n=2), HCM/control siRNA (n=4), HCM/eIF3i siRNA 1# (n=4). *p<0.05, ***p< 0.001. C. Knockdown of eIF3i inhibited tumor induced HUVECs proliferation. CM, conditional medium. (n=3). D. eIF3i loss-of-function inhibits tumorigenic angiogenesis in zebrafish B16-RFP melanoma cells xenografts. The red channel represents tumor, and the green channel represents the blood vessels. The white arrowheads point to endothelial cell migrated into tumor mass. Scale bars, 500μm. EXPRESSION / LABELING:
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