Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1782290988285296640 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3826994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT lijarod theoncogenictbx3isadownstreamtargetandmediatorofthetgfb1signalingpathway AT weinbergmarcs theoncogenictbx3isadownstreamtargetandmediatorofthetgfb1signalingpathway AT zerbiniluiz theoncogenictbx3isadownstreamtargetandmediatorofthetgfb1signalingpathway AT princesharon theoncogenictbx3isadownstreamtargetandmediatorofthetgfb1signalingpathway AT lijarod oncogenictbx3isadownstreamtargetandmediatorofthetgfb1signalingpathway AT weinbergmarcs oncogenictbx3isadownstreamtargetandmediatorofthetgfb1signalingpathway AT zerbiniluiz oncogenictbx3isadownstreamtargetandmediatorofthetgfb1signalingpathway AT princesharon oncogenictbx3isadownstreamtargetandmediatorofthetgfb1signalingpathway |