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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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