Angiogenic sprouting is regulated by endothelial cell expression of Slug

Katrina M. Welch-Reardon, Seema M. Ehsan, Kehui Wang, Nan Wu, Andrew C. Newman, Monica Romero-Lopez, Ashley H. Fong, Steven George, Robert A. Edwards, Christopher C.W. Hughes

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The Snail family of zinc-finger transcription factors are evolutionarily conserved proteins that control processes requiring cell movement. Specifically, they regulate epithelial-to-mesenchymal transitions (EMT) where an epithelial cell severs intercellular junctions, degrades basement membrane and becomes a migratory, mesenchymal-like cell. Interestingly, Slug expression has been observed in angiogenic endothelial cells (EC) in vivo, suggesting that angiogenic sprouting may share common attributes with EMT. Here, we demonstrate that sprouting EC in vitro express both Slug and Snail, and that siRNAmediated knockdown of either inhibits sprouting and migration in multiple in vitro angiogenesis assays. We find that expression of MT1-MMP, but not of VE-Cadherin, is regulated by Slug and that loss of sprouting as a consequence of reduced Slug expression can be reversed by lentiviral-mediated re-expression of MT1-MMP. Activity of MMP2 and MMP9 are also affected by Slug expression, likely through MT1-MMP. Importantly, we find enhanced expression of Slug in EC in human colorectal cancer samples compared with normal colon tissue, suggesting a role for Slug in pathological angiogenesis. In summary, these data implicate Slug as an important regulator of sprouting angiogenesis, particularly in pathological settings.

Original languageEnglish (US)
Pages (from-to)2017-2028
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number9
DOIs
StatePublished - Jan 1 2014

Keywords

  • Angiogenesis
  • Emt
  • Endmt
  • Mmp
  • Mt1-Mmp
  • Snai1
  • Snai2

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Welch-Reardon, K. M., Ehsan, S. M., Wang, K., Wu, N., Newman, A. C., Romero-Lopez, M., Fong, A. H., George, S., Edwards, R. A., & Hughes, C. C. W. (2014). Angiogenic sprouting is regulated by endothelial cell expression of Slug. Journal of Cell Science, 127(9), 2017-2028. https://doi.org/10.1242/jcs.143420