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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#_4 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#_3 http://www.w3.org/ns/prov#value In human endothelial tumors like angiosarcoma or in hemangiomas where the vascular structures are profoundly altered, VE-cadherin is poorly expressed or is frequently misplaced from cell-cell contacts (1). In addition, endothelial cells differentiating in vitro from embryonic stem cells in which VE-cadherin gene has been inactivated form cell aggregates but are unable to organize vascular structures (D. Vittet, T. Bouchou, E. Dejana, and P. Huber manuscript in preparation). These observations indirectly suggest that VE-cadherin and adherens junctions in general contribute to a correct vascular morphogenesis, but the question of what mechanisms are responsible for the process remains unanswered. To form new vessels endothelial cells need to detach from the vascular wall, invade the underlying tissues, and then form tubes which branch and organize into extensive anastomotic networks. This process is complex and involves not only endothelial cell proliferation and migration but also cell-cell and cell-matrix adhesion, proteolytic remodeling of the matrix and changes in integrin expression. These activities need to be strictly controlled for a normal development of the vascular network. For instance, if endothelial cell proliferation or matrix proteolysis is not balanced, the vasculature becomes abnormal with the formation of vascular malformations. Our hypothesis is that VE-cadherin and adherens junctions in general, may play a role in vascular remodeling by controlling and limiting endothelial cell migration and growth and possibly other specific endothelial cell functions. During the first steps of angiogenesis, junctions need to become looser to let cells migrate and invade the underlying tissues. Since VE-cadherin inhibits cell migration from a monolayer (13), endothelial cell detachment from neighboring cells should be preceded by inactivation of VE-cadherin and adherens junctions in general. Indeed, in other types of cells, growth factors such as epithelial growth factor (EGF) and hepatocyte growth factor (HGF) induce tyrosine phosphorylation of adherens junctions components(19) and this effect is related to their cell scattering activity. Angiogenic factors as vascular endothelial growth factor (VEGF) act in a similar way inducing tyrosine phosphorylation of adherens junctions to allow endothelial cell motility (S. Esser, E. Dejana and W. Risau, manuscript in preparation). Interestingly, VEGF is known to increase endothelial cell permeability, and this effect may reflect, at least in part, a weakening of intercellular junctions. http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#_3 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/9413393 http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#_4 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/9413393 http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#_3 http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg#pubinfo http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg http://purl.org/dc/terms/created 2014-07-03T14:34:03.328+02:00 http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RA2KrG2jDRswtgGdzu2Jha3G26emamkqXlXZvWqrtz1Xg http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234