Dissecting the role of endothelial Survivin ΔEx3 in angiogenesis

Hugo Caldas, Jason R. Fangusaro, Daniel R. Boué, Michael P. Holloway, Rachel A. Altura*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Scopus citations

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 ΔEx3 in angiogenesis. We show by confocal microscopy that a pool of endothelial Survivin ΔEx3 is localized to membrane ruffles. We also demonstrate that Survivin ΔEx3 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 ΔEx3 may regulate angiogenesis via several mechanisms including cell invasion, migration, and Rac1 activation. Our findings identify a novel pathway regulating angiogenesis through Survivin ΔEx3 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.

Original languageEnglish (US)
Pages (from-to)1479-1489
Number of pages11
JournalBlood
Volume109
Issue number4
DOIs
StatePublished - Feb 15 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Caldas, H., Fangusaro, J. R., Boué, D. R., Holloway, M. P., & Altura, R. A. (2007). Dissecting the role of endothelial Survivin ΔEx3 in angiogenesis. Blood, 109(4), 1479-1489. https://doi.org/10.1182/blood-2006-02-003749