title: Notch signaling mediates TGF-β1-induced epithelial-mesenchymal transition through the induction of Snai1.
abstract: Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells undergo phenotypic transition to mesenchymal cells and thus is involved in the pathogenesis of tumor metastasis and organ fibrosis. Notch signaling is a highly conserved pathway that regulates intercellular communication and directs cell fate decisions. Here, we show the critical role of Notch signaling in TGF-β1-induced EMT. Inhibition of Notch signaling either by γ-secretase inhibitor or by knocking down of Notch signaling molecules by small interfering RNA abrogated EMT in association with decreased expression of Snai1. Constitutive activation of Notch signaling was sufficient for the induction of Snai1 as well as Notch ligand Jagged1. Notch signaling induced Snai1 expression via direct transcriptional activation. Collectively, these data show that Notch signaling activation promote TGF-β1-induced EMT through the induction of Snai1. Further studies on Notch signaling may provide diagnostic and therapeutic targets for cancer and fibrotic disease.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. yosukem@umich.edu
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Coelho
authors.forename: Gabor
authors.initials: G
authors.lastname: Jarai
authors.forename: John
authors.initials: J
authors.lastname: Westwick
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051880:Receptors, Notch; C000604407:SNAI1 protein, human; D000072099:Serrate-Jagged Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1