Role of scleraxis in regulating snai1 gene expression and its effect on epithelial –mesenchymal transition

dc.contributor.authorAl Hattab, Danah
dc.contributor.examiningcommitteeKardami, Elissavet (Physiology and Pathophysiology) Halayko, Andrew (Physiology and Pathophysiology) Wigle, Jeffrey (Biochemistry and Medical Genetics)en_US
dc.contributor.supervisorCzubryt, Michael (Physiology and Pathophysiology)en_US
dc.date.accessioned2018-01-09T18:44:43Z
dc.date.available2018-01-09T18:44:43Z
dc.date.issued2017
dc.degree.disciplinePhysiology and Pathophysiologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractEpithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their ability for cell to cell adhesion, causing a pheno-conversion of epithelial cells into the migratory phenotype of mesenchymal cells. EMT is induced in part by Snai1 expression which directly represses E-Cadherin transcription. E-Cadherin plays an integral role in forming adherens junctions that bind cells together. The EMT process plays an essential role in physiological trans-differentiation of cells during development and contributes to pathological responses and cancer progression. Snai1 is a zinc-finger transcription factor that triggers EMT during embryonic development as well as in pathological processes such as tumors or fibrosis. Scleraxis is a transcription factor that significantly increases the expression of important extracellular matrix genes such as type I collagen and the contractile protein α-smooth muscle actin (α -SMA), which are key players of the fibrotic process. Our published data suggests that Scleraxis overexpression in the adenocarcinomic human alveolar basal epithelial cells (A549 cells) down-regulates some epithelial markers while up-regulating mesenchymal markers, thus contributing to EMT. Here we show that Scleraxis regulates the transcriptional activity of the Snai1 gene through direct binding to E-box sequences within its promoter. Additionally, we show that Scleraxis enhances EMT progression mediated by its interaction with the Snai1 gene promoter. These findings suggest that Scleraxis –Snai1 axis is a potential therapeutic candidate that could be targeted in pathological processes where EMT is elevated.en_US
dc.description.noteFebruary 2018en_US
dc.identifier.urihttp://hdl.handle.net/1993/32750
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectScleraxisen_US
dc.subjectSnai1en_US
dc.subjectEpithelial- mesenchymal transitionen_US
dc.titleRole of scleraxis in regulating snai1 gene expression and its effect on epithelial –mesenchymal transitionen_US
dc.typemaster thesisen_US
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