Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3.
Mutations in CCM1, CCM2, or CCM3 lead to cerebral cavernous malformations, one of the most common hereditary vascular diseases of the brain. Endothelial cells within these lesions are the main disease compartments. Here, we show that adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures. Adenoviral CCM3 expression does not induce apoptosis under normal endothelial cell culture conditions but protects endothelial cells from staurosporine-induced cell death. Tyrosine kinase activity profiling suggests that CCM3 supports PDPK-1/Akt-mediated endothelial cell quiescence and survival.
Schleider
Elisa
E
Department of Human Genetics, University of Würzburg, Würzburg, Germany.
Stahl
Sonja
S
Wüstehube
Joycelyn
J
Walter
Ulrich
U
Fischer
Andreas
A
Felbor
Ute
U
D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000502:physiology*; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D020786:Hemangioma, Cavernous, Central Nervous System / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D019311:Staurosporine