Role of Survivin‐ exon3 in angiogenesis

The complexities of the Survivin family of proteins has greatly increased since the identification of alternative splice variants generated from the genomic locus that possess distinct functions from those originally identified for the main Survivin isoform. Previous studies on the functions of Survivin splice variants have been performed almost exclusively within cancer cells, however Survivin has increasingly been implicated in other physiological and pathophysiological processes, including angiogenesis. In this study we dissect the involvement of the Survivin family of proteins in the mediation of angiogenesis. We show by confocal microscopy that a pool of endothelial Survivin‐Δexon3 is localized to membrane ruffles. We also demonstrate that Survivin‐Δexon3 is the Survivin splice variant responsible for modulation of angiogenesis in vitro in tube formation assays and in vivo by direct in vivo angiogenesis assay. Our data indicate that Survivin‐Δexon3 may regulate angiogenesis via several mechanisms including cell invasion, migration and Rac activation. Our findings identify a novel pathway regulating angiogenesis through Survivin‐Δexon3 and a novel mechanism for Rac activation during angiogenesis. In conclusion, our results provide new insight into the regulation of endothelial cell homeostasis and angiogenesis by the Survivin family.