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The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway

The T-box transcription factor, TBX3, plays an important role in embryonic development, and haploinsufficiency of TBX3 causes ulnar–mammary syndrome. Overexpression of TBX3, on the other hand, is associated with several cancers, and preliminary evidence suggests that increased levels of TBX3 may inh...

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Autores principales: Li, Jarod, Weinberg, Marc S., Zerbini, Luiz, Prince, Sharon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826994/
https://www.ncbi.nlm.nih.gov/pubmed/24025717
http://dx.doi.org/10.1091/mbc.E13-05-0273
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author Li, Jarod
Weinberg, Marc S.
Zerbini, Luiz
Prince, Sharon
author_facet Li, Jarod
Weinberg, Marc S.
Zerbini, Luiz
Prince, Sharon
author_sort Li, Jarod
collection PubMed
description The T-box transcription factor, TBX3, plays an important role in embryonic development, and haploinsufficiency of TBX3 causes ulnar–mammary syndrome. Overexpression of TBX3, on the other hand, is associated with several cancers, and preliminary evidence suggests that increased levels of TBX3 may inhibit cell proliferation but promote tumor migration and invasion. Although this suggests that deregulated levels of TBX3 are deleterious in development and promotes disease, very little is known about the signaling pathways that regulate TBX3 expression. Here we show that overexpressing TBX3 inhibits proliferative ability while promoting the migration of breast epithelial cells. We demonstrate that the transforming growth factor β1 (TGF-β1) pathway up-regulates TBX3 protein and mRNA levels and show a detailed transcriptional mechanism by which this occurs. Using in vitro and in vivo assays, we show that Smad3/4 and JunB bind and cooperatively regulate TBX3 promoter activity through a Smad-binding element at −67 base pairs. Further, we show that TBX3 plays a pivotal role in mediating the antiproliferative and promigratory role of TGF-β1 in breast epithelial and skin keratinocytes. This study identifies the TGF-β1 signaling pathway as a potentially important player in the regulation of TBX3 in development and cancer.
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spelling pubmed-38269942014-01-30 The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway Li, Jarod Weinberg, Marc S. Zerbini, Luiz Prince, Sharon Mol Biol Cell Articles The T-box transcription factor, TBX3, plays an important role in embryonic development, and haploinsufficiency of TBX3 causes ulnar–mammary syndrome. Overexpression of TBX3, on the other hand, is associated with several cancers, and preliminary evidence suggests that increased levels of TBX3 may inhibit cell proliferation but promote tumor migration and invasion. Although this suggests that deregulated levels of TBX3 are deleterious in development and promotes disease, very little is known about the signaling pathways that regulate TBX3 expression. Here we show that overexpressing TBX3 inhibits proliferative ability while promoting the migration of breast epithelial cells. We demonstrate that the transforming growth factor β1 (TGF-β1) pathway up-regulates TBX3 protein and mRNA levels and show a detailed transcriptional mechanism by which this occurs. Using in vitro and in vivo assays, we show that Smad3/4 and JunB bind and cooperatively regulate TBX3 promoter activity through a Smad-binding element at −67 base pairs. Further, we show that TBX3 plays a pivotal role in mediating the antiproliferative and promigratory role of TGF-β1 in breast epithelial and skin keratinocytes. This study identifies the TGF-β1 signaling pathway as a potentially important player in the regulation of TBX3 in development and cancer. The American Society for Cell Biology 2013-11-15 /pmc/articles/PMC3826994/ /pubmed/24025717 http://dx.doi.org/10.1091/mbc.E13-05-0273 Text en © 2013 Li et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Li, Jarod
Weinberg, Marc S.
Zerbini, Luiz
Prince, Sharon
The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway
title The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway
title_full The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway
title_fullStr The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway
title_full_unstemmed The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway
title_short The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway
title_sort oncogenic tbx3 is a downstream target and mediator of the tgf-β1 signaling pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826994/
https://www.ncbi.nlm.nih.gov/pubmed/24025717
http://dx.doi.org/10.1091/mbc.E13-05-0273
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