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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...

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Autores principales: Thuault, Sylvie, Valcourt, Ulrich, Petersen, Maj, Manfioletti, Guidalberto, Heldin, Carl-Henrik, Moustakas, Aristidis
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
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.
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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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