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Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation
The mitogen-inducible gene 6 (MIG6) is an adaptor protein widely expressed in vascular endothelial cells. However, it remains unknown thus far whether it plays a role in angiogenesis. Here, using comprehensive in vitro and in vivo model systems, we unveil a potent anti-angiogenic effect of MIG6 in r...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937727/ https://www.ncbi.nlm.nih.gov/pubmed/33693003 http://dx.doi.org/10.3389/fcell.2021.634242 |
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author | Liu, Lixian Xing, Liying Chen, Rongyuan Zhang, Jianing Huang, Yuye Huang, Lijuan Xie, Bingbing Ren, Xiangrong Wang, Shasha Kuang, Haiqing Lin, Xianchai Kumar, Anil Kim, Jong Kyong Lee, Chunsik Li, Xuri |
author_facet | Liu, Lixian Xing, Liying Chen, Rongyuan Zhang, Jianing Huang, Yuye Huang, Lijuan Xie, Bingbing Ren, Xiangrong Wang, Shasha Kuang, Haiqing Lin, Xianchai Kumar, Anil Kim, Jong Kyong Lee, Chunsik Li, Xuri |
author_sort | Liu, Lixian |
collection | PubMed |
description | The mitogen-inducible gene 6 (MIG6) is an adaptor protein widely expressed in vascular endothelial cells. However, it remains unknown thus far whether it plays a role in angiogenesis. Here, using comprehensive in vitro and in vivo model systems, we unveil a potent anti-angiogenic effect of MIG6 in retinal development and neovascularization and the underlying molecular and cellular mechanisms. Loss of function assays using genetic deletion of Mig6 or siRNA knockdown increased angiogenesis in vivo and in vitro, while MIG6 overexpression suppressed pathological angiogenesis. Moreover, we identified the cellular target of MIG6 by revealing its direct inhibitory effect on vascular endothelial cells (ECs). Mechanistically, we found that the anti-angiogenic effect of MIG6 is fulfilled by binding to SHC1 and inhibiting its phosphorylation. Indeed, SHC1 knockdown markedly diminished the effect of MIG6 on ECs. Thus, our findings show that MIG6 is a potent endogenous inhibitor of angiogenesis that may have therapeutic value in anti-angiogenic therapy. |
format | Online Article Text |
id | pubmed-7937727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79377272021-03-09 Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation Liu, Lixian Xing, Liying Chen, Rongyuan Zhang, Jianing Huang, Yuye Huang, Lijuan Xie, Bingbing Ren, Xiangrong Wang, Shasha Kuang, Haiqing Lin, Xianchai Kumar, Anil Kim, Jong Kyong Lee, Chunsik Li, Xuri Front Cell Dev Biol Cell and Developmental Biology The mitogen-inducible gene 6 (MIG6) is an adaptor protein widely expressed in vascular endothelial cells. However, it remains unknown thus far whether it plays a role in angiogenesis. Here, using comprehensive in vitro and in vivo model systems, we unveil a potent anti-angiogenic effect of MIG6 in retinal development and neovascularization and the underlying molecular and cellular mechanisms. Loss of function assays using genetic deletion of Mig6 or siRNA knockdown increased angiogenesis in vivo and in vitro, while MIG6 overexpression suppressed pathological angiogenesis. Moreover, we identified the cellular target of MIG6 by revealing its direct inhibitory effect on vascular endothelial cells (ECs). Mechanistically, we found that the anti-angiogenic effect of MIG6 is fulfilled by binding to SHC1 and inhibiting its phosphorylation. Indeed, SHC1 knockdown markedly diminished the effect of MIG6 on ECs. Thus, our findings show that MIG6 is a potent endogenous inhibitor of angiogenesis that may have therapeutic value in anti-angiogenic therapy. Frontiers Media S.A. 2021-02-22 /pmc/articles/PMC7937727/ /pubmed/33693003 http://dx.doi.org/10.3389/fcell.2021.634242 Text en Copyright © 2021 Liu, Xing, Chen, Zhang, Huang, Huang, Xie, Ren, Wang, Kuang, Lin, Kumar, Kim, Lee and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Liu, Lixian Xing, Liying Chen, Rongyuan Zhang, Jianing Huang, Yuye Huang, Lijuan Xie, Bingbing Ren, Xiangrong Wang, Shasha Kuang, Haiqing Lin, Xianchai Kumar, Anil Kim, Jong Kyong Lee, Chunsik Li, Xuri Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation |
title | Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation |
title_full | Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation |
title_fullStr | Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation |
title_full_unstemmed | Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation |
title_short | Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation |
title_sort | mitogen-inducible gene 6 inhibits angiogenesis by binding to shc1 and suppressing its phosphorylation |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937727/ https://www.ncbi.nlm.nih.gov/pubmed/33693003 http://dx.doi.org/10.3389/fcell.2021.634242 |
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