VE-cadherin expression and clustering maintain low levels of survivin in endothelial cells

Am J Pathol. 2004 Jul;165(1):181-9. doi: 10.1016/S0002-9440(10)63287-7.


Survivin is strongly expressed in embryonic organs and in tumor cells but is low or absent in differentiated normal tissues. Resting endothelium expresses low levels of survivin but can up-regulate its synthesis on activation to proliferate. The mechanisms responsible for survivin down-regulation in resting conditions are still unknown. We report here that confluence and vascular endothelial-cadherin (VE-cadherin) expression induce contact inhibition of cell growth and survivin down-regulation in the endothelium. Using beta-catenin null and positive isogenic endothelial cell lines we found that the effect requires beta-catenin expression and its association to VE-cadherin cytoplasmic tail. Furthermore, in allantois organ cultures, survivin expression is up-regulated in areas of growing vessels where VE-cadherin is partially dismantled from junctions or in VE-cadherin -/- specimens. Overall, these data indicate that VE-cadherin and beta-catenin may negatively regulate survivin synthesis in endothelial cells. Consistently, in epidermal and pancreatic cell lines or ovarian tumors, epithelial-cadherin (E-cadherin) and survivin expression is inversely related, suggesting a non-cell-specific role of cadherins in reducing survivin synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allantois / cytology
  • Animals
  • Antigens, CD
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Division
  • Cell Line
  • Cell Line, Tumor
  • Cluster Analysis
  • Cytoskeletal Proteins
  • Down-Regulation
  • Embryo, Mammalian
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Fibronectins / metabolism
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Luminescent Proteins
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Neoplasm Proteins
  • Neovascularization, Physiologic / physiology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Stem Cells / cytology
  • Survivin
  • Trans-Activators
  • Umbilical Veins / cytology
  • Up-Regulation
  • beta Catenin


  • Antigens, CD
  • BIRC5 protein, human
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • Fibronectins
  • Inhibitor of Apoptosis Proteins
  • Luminescent Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Survivin
  • Trans-Activators
  • beta Catenin
  • cadherin 5
  • Green Fluorescent Proteins