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Published on: March 30, 2019
Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation
Lixian Liu1, Liying Xing1, Rongyuan Chen1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Insights
Mitogen-inducible gene 6 (MIG6) inhibits blood vessel formation. This study reveals MIG6
Area of Science:
- Molecular Biology
- Cell Biology
- Vascular Biology
Background:
- Mitogen-inducible gene 6 (MIG6) is an adaptor protein found in vascular endothelial cells.
- The role of MIG6 in angiogenesis, the formation of new blood vessels, is currently unknown.
Purpose of the Study:
- To investigate the function of MIG6 in retinal development and neovascularization.
- To elucidate the molecular and cellular mechanisms underlying MIG6's effect on angiogenesis.
Main Methods:
- Utilized in vitro and in vivo model systems to study angiogenesis.
- Performed loss-of-function assays (genetic deletion, siRNA knockdown) and overexpression studies.
- Investigated the interaction between MIG6 and SHC1 in endothelial cells (ECs).
Main Results:
- Loss of MIG6 function led to increased angiogenesis in vitro and in vivo.
- MIG6 overexpression suppressed pathological angiogenesis.
- MIG6 directly inhibits vascular endothelial cells by binding to and inhibiting SHC1 phosphorylation.
Conclusions:
- MIG6 acts as a potent endogenous inhibitor of angiogenesis.
- MIG6's anti-angiogenic effect is mediated through the SHC1 pathway.
- MIG6 holds potential therapeutic value for anti-angiogenic therapies.
Abstract:
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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