Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels

Sarah M. Taylor, Kathleen R. Nevis, Hannah L. Park, Gregory C. Rogers, Stephen L. Rogers, Jeanette G. Cook, Victoria L. Bautch

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Regulated vascular endothelial growth factor (VEGF) signaling is required for proper angiogenesis, and excess VEGF signaling results in aberrantly formed vessels that do not function properly. Tumor endothelial cells have excess centrosomes and are aneuploid, properties that probably contribute to the morphologic and functional abnormalities of tumor vessels. We hypothesized that endothelial cell centrosome number is regulated by signaling via angiogenic factors, such as VEGF. We found that endothelial cells in developing vessels exposed to elevated VEGF signaling display centrosome overduplication. Signaling from VEGF, through either MEK/ERK or AKT to cyclin E/Cdk2, is amplified in association with centrosome overduplication, and blockade of relevant pathway components rescued the centrosome overduplication defect. Endothelial cells exposed to elevated FGF also had excess centrosomes, suggesting that multiple angiogenic factors regulate centrosome number. Endothelial cells with excess centrosomes survived and formed aberrant spindles at mitosis. Developing vessels exposed to elevated VEGF signaling also exhibited increased aneuploidy of endothelial cells, which is associated with cellular dysfunction. These results provide the first link between VEGF signaling and regulation of the centrosome duplication cycle, and suggest that endothelial cell centrosome overduplication contributes to aberrant angiogenesis in developing vessel networks exposed to excess angiogenic factors.

Original languageEnglish (US)
Pages (from-to)3108-3117
Number of pages10
JournalBlood
Volume116
Issue number16
DOIs
StatePublished - Oct 21 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels'. Together they form a unique fingerprint.

  • Cite this

    Taylor, S. M., Nevis, K. R., Park, H. L., Rogers, G. C., Rogers, S. L., Cook, J. G., & Bautch, V. L. (2010). Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels. Blood, 116(16), 3108-3117. https://doi.org/10.1182/blood-2010-01-266197