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Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition
Epithelial–mesenchymal transition (EMT) occurs during embryogenesis, carcinoma invasiveness, and metastasis and can be elicited by transforming growth factor-β (TGF-β) signaling via intracellular Smad transducers. The molecular mechanisms that control the onset of EMT remain largely unexplored. Tran...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064178/ https://www.ncbi.nlm.nih.gov/pubmed/16831886 http://dx.doi.org/10.1083/jcb.200512110 |
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author | Thuault, Sylvie Valcourt, Ulrich Petersen, Maj Manfioletti, Guidalberto Heldin, Carl-Henrik Moustakas, Aristidis |
author_facet | Thuault, Sylvie Valcourt, Ulrich Petersen, Maj Manfioletti, Guidalberto Heldin, Carl-Henrik Moustakas, Aristidis |
author_sort | Thuault, Sylvie |
collection | PubMed |
description | Epithelial–mesenchymal transition (EMT) occurs during embryogenesis, carcinoma invasiveness, and metastasis and can be elicited by transforming growth factor-β (TGF-β) signaling via intracellular Smad transducers. The molecular mechanisms that control the onset of EMT remain largely unexplored. Transcriptomic analysis revealed that the high mobility group A2 (HMGA2) gene is induced by the Smad pathway during EMT. Endogenous HMGA2 mediates EMT by TGF-β, whereas ectopic HMGA2 causes irreversible EMT characterized by severe E-cadherin suppression. HMGA2 provides transcriptional input for the expression control of four known regulators of EMT, the zinc-finger proteins Snail and Slug, the basic helix-loop-helix protein Twist, and inhibitor of differentiation 2. We delineate a pathway that links TGF-β signaling to the control of epithelial differentiation via HMGA2 and a cohort of major regulators of tumor invasiveness and metastasis. This network of signaling/transcription factors that work sequentially to establish EMT suggests that combinatorial detection of these proteins could serve as a new tool for EMT analysis in cancer patients. |
format | Text |
id | pubmed-2064178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20641782007-11-29 Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition Thuault, Sylvie Valcourt, Ulrich Petersen, Maj Manfioletti, Guidalberto Heldin, Carl-Henrik Moustakas, Aristidis J Cell Biol Research Articles Epithelial–mesenchymal transition (EMT) occurs during embryogenesis, carcinoma invasiveness, and metastasis and can be elicited by transforming growth factor-β (TGF-β) signaling via intracellular Smad transducers. The molecular mechanisms that control the onset of EMT remain largely unexplored. Transcriptomic analysis revealed that the high mobility group A2 (HMGA2) gene is induced by the Smad pathway during EMT. Endogenous HMGA2 mediates EMT by TGF-β, whereas ectopic HMGA2 causes irreversible EMT characterized by severe E-cadherin suppression. HMGA2 provides transcriptional input for the expression control of four known regulators of EMT, the zinc-finger proteins Snail and Slug, the basic helix-loop-helix protein Twist, and inhibitor of differentiation 2. We delineate a pathway that links TGF-β signaling to the control of epithelial differentiation via HMGA2 and a cohort of major regulators of tumor invasiveness and metastasis. This network of signaling/transcription factors that work sequentially to establish EMT suggests that combinatorial detection of these proteins could serve as a new tool for EMT analysis in cancer patients. The Rockefeller University Press 2006-07-17 /pmc/articles/PMC2064178/ /pubmed/16831886 http://dx.doi.org/10.1083/jcb.200512110 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Thuault, Sylvie Valcourt, Ulrich Petersen, Maj Manfioletti, Guidalberto Heldin, Carl-Henrik Moustakas, Aristidis Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition |
title | Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition |
title_full | Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition |
title_fullStr | Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition |
title_full_unstemmed | Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition |
title_short | Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition |
title_sort | transforming growth factor-β employs hmga2 to elicit epithelial–mesenchymal transition |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064178/ https://www.ncbi.nlm.nih.gov/pubmed/16831886 http://dx.doi.org/10.1083/jcb.200512110 |
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