title: Tie1 deficiency induces endothelial-mesenchymal transition.
abstract: Endothelial-mesenchymal transition (EndMT) has a significant role in embryonic heart formation and in various pathologies. However, the molecular mechanisms that regulate EndMT induction remain to be elucidated. We show that suppression of receptor tyrosine kinase Tie1 but not Tie2 induces human endothelial cells to undergo EndMT and that Slug deficiency reverts this process. We find that Erk1/2, Erk5 and Akt cascades control Slug promoter activity induced by Tie1 deficiency. Interestingly, EndMT is present in human pancreatic tumour. We propose that EndMT associated with Tie1 downregulation participates in the pathological development of stroma observed in tumours.
authors.affiliation: INSERM U 624, Stress Cellulaire, 163 Avenue de Luminy-Case 915, 13288 Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Garcia
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Sandi
authors.forename: Pierre
authors.initials: P
authors.lastname: Cordelier
authors.forename: Bernard
authors.initials: B
authors.lastname: Binétruy
authors.forename: Jacques
authors.initials: J
authors.lastname: Pouysségur
authors.forename: Juan Lucio
authors.initials: JL
authors.lastname: Iovanna
authors.forename: Roselyne
authors.initials: R
authors.lastname: Tournaire
mesh_terms: D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D054338:Cell Transdifferentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004727:Endothelium / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D042810:Receptor, TIE-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D042810:Receptor, TIE-1