Integration of TGF-β/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition
| العنوان: | Integration of TGF-β/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition |
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| المؤلفون: | Erwin P. Bottinger, Jiri Zavadil, Lukas Cermak, Noemi Soto-Nieves |
| المصدر: | The EMBO Journal. 23:1155-1165 |
| بيانات النشر: | Wiley, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Keratinocytes, JAG1, Transcription, Genetic, Cellular differentiation, Notch signaling pathway, Repressor, Biology, Response Elements, Article, General Biochemistry, Genetics and Molecular Biology, Mesoderm, Mice, Dogs, Cell Movement, Transforming Growth Factor beta, Basic Helix-Loop-Helix Transcription Factors, Cell Adhesion, Animals, Humans, Smad3 Protein, Epithelial–mesenchymal transition, Promoter Regions, Genetic, Molecular Biology, HEY1, Cells, Cultured, Smad4 Protein, Receptors, Notch, General Immunology and Microbiology, General Neuroscience, Membrane Proteins, Cell Differentiation, Epithelial Cells, Transforming growth factor beta, Cadherins, DNA-Binding Proteins, Repressor Proteins, Trans-Activators, Cancer research, biology.protein, Protein Binding, Signal Transduction, Transforming growth factor |
| الوصف: | Epithelial-to-mesenchymal transitions (EMTs) underlie cell plasticity required in embryonic development and frequently observed in advanced carcinogenesis. Transforming growth factor-beta (TGF-beta) induces EMT phenotypes in epithelial cells in vitro and has been associated with EMT in vivo. Here we report that expression of the hairy/enhancer-of-split-related transcriptional repressor Hey1, and the Notch-ligand Jagged1 (Jag1), was induced by TGF-beta at the onset of EMT in epithelial cells from mammary gland, kidney tubules, and epidermis. The HEY1 expression profile was biphasic, consisting of immediate-early Smad3-dependent, Jagged1/Notch-independent activation, followed by delayed, indirect Jagged1/Notch-dependent activation. TGF-beta-induced EMT was blocked by RNA silencing of HEY1 or JAG1, and by chemical inactivation of Notch. The EMT phenotype, biphasic activation of Hey1, and delayed expression of Jag1 were induced by TGF-beta in wild-type, but not in Smad3-deficient, primary mouse kidney tubular epithelial cells. Our findings identify a new mechanism for functional integration of Jagged1/Notch signalling and coordinated activation of the Hey1 transcriptional repressor controlled by TGF-beta/Smad3, and demonstrate functional roles for Smad3, Hey1, and Jagged1/Notch in mediating TGF-beta-induced EMT. |
| تدمد: | 1460-2075 0261-4189 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53268f321e6cc7e9a4aa03a0b6bcc1d1Test https://doi.org/10.1038/sj.emboj.7600069Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....53268f321e6cc7e9a4aa03a0b6bcc1d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602075 02614189 |
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