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The inhibition of protein translation promotes tumor angiogenic switch

The ‘angiogenic switch’ is critical for tumor progression. However, the pathological details and molecular mechanisms remain incompletely characterized. In this study, we established mammal xenografts in zebrafish to visually investigate the first vessel growth (angiogenic switch) in real-time, by i...

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Autores principales: Luo, Hui, Shen, Yuge, Liao, Weiting, Li, Qiqi, Wu, Ni, Zhong, Jian, Xiao, Chaoxin, Gan, Jia, Yang, Yun, Dong, E., Zhang, Guimin, Liu, Binrui, Yue, Xiaozhu, Xu, Lin, Liu, Yan, Zhao, Chengjian, Zhong, Qian, Yang, Hanshuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192909/
https://www.ncbi.nlm.nih.gov/pubmed/35695994
http://dx.doi.org/10.1186/s43556-022-00081-4
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author Luo, Hui
Shen, Yuge
Liao, Weiting
Li, Qiqi
Wu, Ni
Zhong, Jian
Xiao, Chaoxin
Gan, Jia
Yang, Yun
Dong, E.
Zhang, Guimin
Liu, Binrui
Yue, Xiaozhu
Xu, Lin
Liu, Yan
Zhao, Chengjian
Zhong, Qian
Yang, Hanshuo
author_facet Luo, Hui
Shen, Yuge
Liao, Weiting
Li, Qiqi
Wu, Ni
Zhong, Jian
Xiao, Chaoxin
Gan, Jia
Yang, Yun
Dong, E.
Zhang, Guimin
Liu, Binrui
Yue, Xiaozhu
Xu, Lin
Liu, Yan
Zhao, Chengjian
Zhong, Qian
Yang, Hanshuo
author_sort Luo, Hui
collection PubMed
description The ‘angiogenic switch’ is critical for tumor progression. However, the pathological details and molecular mechanisms remain incompletely characterized. In this study, we established mammal xenografts in zebrafish to visually investigate the first vessel growth (angiogenic switch) in real-time, by inoculating tumor cells into the perivitelline space of live optically transparent Transgenic (flk1:EGFP) zebrafish larvae. Using this model, we found that hypoxia and hypoxia-inducible factor (HIF) signaling were unnecessary for the angiogenic switch, whereas vascular endothelial growth factor A gene (Vegfa) played a crucial role. Mechanistically, transcriptome analysis showed that the angiogenic switch was characterized by inhibition of translation, but not hypoxia. Phosphorylation of eukaryotic translation initiation factor 2 alpha (Eif2α) and the expression of Vegfa were increased in the angiogenic switch microtumors, and 3D tumor spheroids, and puromycin-treated tumor cells. Vegfa overexpression promoted early onset of the angiogenic switch, whereas Vegfa knockout prevented the first tumor vessel from sprouting. Pretreatment of tumor cells with puromycin promoted the angiogenic switch in vivo similarly to Vegfa overexpression, whereas Vegfa knockdown suppressed the increase. This study provides direc and dynamic in vivo evidences that inhibition of translation, but not hypoxia or HIF signaling promotes the angiogenic switch in tumor by increasing Vegfa transcription. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43556-022-00081-4.
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spelling pubmed-91929092022-06-15 The inhibition of protein translation promotes tumor angiogenic switch Luo, Hui Shen, Yuge Liao, Weiting Li, Qiqi Wu, Ni Zhong, Jian Xiao, Chaoxin Gan, Jia Yang, Yun Dong, E. Zhang, Guimin Liu, Binrui Yue, Xiaozhu Xu, Lin Liu, Yan Zhao, Chengjian Zhong, Qian Yang, Hanshuo Mol Biomed Research The ‘angiogenic switch’ is critical for tumor progression. However, the pathological details and molecular mechanisms remain incompletely characterized. In this study, we established mammal xenografts in zebrafish to visually investigate the first vessel growth (angiogenic switch) in real-time, by inoculating tumor cells into the perivitelline space of live optically transparent Transgenic (flk1:EGFP) zebrafish larvae. Using this model, we found that hypoxia and hypoxia-inducible factor (HIF) signaling were unnecessary for the angiogenic switch, whereas vascular endothelial growth factor A gene (Vegfa) played a crucial role. Mechanistically, transcriptome analysis showed that the angiogenic switch was characterized by inhibition of translation, but not hypoxia. Phosphorylation of eukaryotic translation initiation factor 2 alpha (Eif2α) and the expression of Vegfa were increased in the angiogenic switch microtumors, and 3D tumor spheroids, and puromycin-treated tumor cells. Vegfa overexpression promoted early onset of the angiogenic switch, whereas Vegfa knockout prevented the first tumor vessel from sprouting. Pretreatment of tumor cells with puromycin promoted the angiogenic switch in vivo similarly to Vegfa overexpression, whereas Vegfa knockdown suppressed the increase. This study provides direc and dynamic in vivo evidences that inhibition of translation, but not hypoxia or HIF signaling promotes the angiogenic switch in tumor by increasing Vegfa transcription. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43556-022-00081-4. Springer Nature Singapore 2022-06-13 /pmc/articles/PMC9192909/ /pubmed/35695994 http://dx.doi.org/10.1186/s43556-022-00081-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Luo, Hui
Shen, Yuge
Liao, Weiting
Li, Qiqi
Wu, Ni
Zhong, Jian
Xiao, Chaoxin
Gan, Jia
Yang, Yun
Dong, E.
Zhang, Guimin
Liu, Binrui
Yue, Xiaozhu
Xu, Lin
Liu, Yan
Zhao, Chengjian
Zhong, Qian
Yang, Hanshuo
The inhibition of protein translation promotes tumor angiogenic switch
title The inhibition of protein translation promotes tumor angiogenic switch
title_full The inhibition of protein translation promotes tumor angiogenic switch
title_fullStr The inhibition of protein translation promotes tumor angiogenic switch
title_full_unstemmed The inhibition of protein translation promotes tumor angiogenic switch
title_short The inhibition of protein translation promotes tumor angiogenic switch
title_sort inhibition of protein translation promotes tumor angiogenic switch
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192909/
https://www.ncbi.nlm.nih.gov/pubmed/35695994
http://dx.doi.org/10.1186/s43556-022-00081-4
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