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Published on: June 30, 2023
Dissecting the role of endothelial SURVIVIN DeltaEx3 in angiogenesis
Hugo Caldas1, Jason R Fangusaro, Daniel R Boué
1Center for Childhood Cancer, Columbus Children's Research Institute, OH 43205, USA.
Abstract:
The identification of alternative splice variants of Survivin that possess distinct functions from those originally identified for the main Survivin isoform has greatly increased the complexity of our understanding of the role of Survivin in different cells. Previous functional studies of the Survivin splice variants have been performed almost exclusively in cancer cells. However, Survivin has increasingly been implicated in other normal physiologic and pathophysiologic processes, including angiogenesis. In this study, we dissect the involvement of Survivin DeltaEx3 in angiogenesis. We show by confocal microscopy that a pool of endothelial Survivin DeltaEx3 is localized to membrane ruffles. We also demonstrate that Survivin DeltaEx3 is the Survivin splice variant responsible for modulating angiogenesis in vitro, in tube formation assays, and in vivo, in an in vivo angiogenesis assay. Our data indicate that Survivin DeltaEx3 may regulate angiogenesis via several mechanisms including cell invasion, migration, and Rac1 activation. Our findings identify a novel pathway regulating angiogenesis through Survivin DeltaEx3 and a novel mechanism for Rac1 activation during angiogenesis. In conclusion, our results provide new insights into the regulation of endothelial cell homeostasis and angiogenesis by the Survivin proteins.
Insights
Survivin DeltaEx3, a splice variant, is crucial for angiogenesis by influencing endothelial cell migration and invasion. This study reveals a new pathway for regulating blood vessel formation.
Area of Science:
- Molecular Biology
- Cell Biology
- Physiology
Background:
- Survivin splice variants have distinct functions, complicating understanding of Survivin's role.
- Previous studies focused on cancer cells, but Survivin is implicated in normal processes like angiogenesis.
- The specific role of Survivin DeltaEx3 in angiogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the involvement of Survivin DeltaEx3 in angiogenesis.
- To determine the mechanisms by which Survivin DeltaEx3 modulates endothelial cell behavior.
- To identify novel pathways regulating angiogenesis.
Main Methods:
- Confocal microscopy to localize Survivin DeltaEx3 in endothelial cells.
- In vitro tube formation assays to assess angiogenesis.
- In vivo angiogenesis assays to evaluate blood vessel formation.
- Analysis of cell invasion, migration, and Rac1 activation.
Main Results:
- Survivin DeltaEx3 localizes to membrane ruffles in endothelial cells.
- Survivin DeltaEx3 significantly modulates angiogenesis in vitro and in vivo.
- Mechanisms include regulation of cell invasion, migration, and Rac1 activation.
- A novel pathway for Rac1 activation during angiogenesis was identified.
Conclusions:
- Survivin DeltaEx3 is a key regulator of angiogenesis.
- The protein influences endothelial cell homeostasis through invasion, migration, and Rac1 activation.
- This research uncovers a new mechanism for Rac1 activation in angiogenesis.
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