VE-cadherin expression and clustering maintain low levels of survivin in endothelial cells.
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.
Iurlaro
Monica
M
Italian Foundation for Cancer Research, Institute of Molecular Oncology, Milan, Italy.
Demontis
Fabio
F
Corada
Monica
M
Zanetta
Lucia
L
Drake
Cristopher
C
Gariboldi
Manuela
M
Peiro
Sandra
S
Cano
Amparo
A
Navarro
Pilar
P
Cattelino
Anna
A
Tognin
Simona
S
Marchisio
Pier Carlo
PC
Dejana
Elisabetta
E
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
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