title: VE-cadherin expression and clustering maintain low levels of survivin in endothelial cells.
abstract: 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.
authors.affiliation: Italian Foundation for Cancer Research, Institute of Molecular Oncology, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Iurlaro
authors.forename: Fabio
authors.initials: F
authors.lastname: Demontis
authors.forename: Monica
authors.initials: M
authors.lastname: Corada
authors.forename: Lucia
authors.initials: L
authors.lastname: Zanetta
authors.forename: Cristopher
authors.initials: C
authors.lastname: Drake
authors.forename: Manuela
authors.initials: M
authors.lastname: Gariboldi
authors.forename: Sandra
authors.initials: S
authors.lastname: Peiro
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: Pilar
authors.initials: P
authors.lastname: Navarro
authors.forename: Anna
authors.initials: A
authors.lastname: Cattelino
authors.forename: Simona
authors.initials: S
authors.lastname: Tognin
authors.forename: Pier Carlo
authors.initials: PC
authors.lastname: Marchisio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
mesh_terms: D000482:Allantois / Q000166:cytology; D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003598:Cytoskeletal Proteins; D015536:Down-Regulation; D004622:Embryo, Mammalian; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008164:Luminescent Proteins; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins; D018919:Neovascularization, Physiologic / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D000077022:Survivin; D015534:Trans-Activators; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D051176:beta Catenin; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D049452:Green Fluorescent Proteins; D051034:Inhibitor of Apoptosis Proteins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000077022:Survivin; D015534:Trans-Activators; D051176:beta Catenin; D000099152:Cadherin 5; C107489:BIRC5 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse