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The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis
The AKT3 signalling pathway plays a critical role in melanoma formation and invasion and components of this signalling cascade are therefore attractive targets for the treatment of malignant melanoma. Recent evidence show that the embryonically important TBX3 transcription factor is upregulated in a...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359334/ https://www.ncbi.nlm.nih.gov/pubmed/25595898 |
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author | Peres, Jade Mowla, Shaheen Prince, Sharon |
author_facet | Peres, Jade Mowla, Shaheen Prince, Sharon |
author_sort | Peres, Jade |
collection | PubMed |
description | The AKT3 signalling pathway plays a critical role in melanoma formation and invasion and components of this signalling cascade are therefore attractive targets for the treatment of malignant melanoma. Recent evidence show that the embryonically important TBX3 transcription factor is upregulated in a subset of melanomas and plays a key role in promoting melanoma formation and invasion, in part by repressing the cell adhesion molecule E-cadherin. We have identified TBX3 as a key substrate of AKT3 in melanomagenesis. Briefly, using site-directed mutagenesis and in vitro kinase assays, we have identified the AKT3 target site at serine residue 720 in the TBX3 protein and show that this site is phosphorylated in vivo. Importantly, we show by western blotting, immunofluorescence, reporter, migration and invasion assays that the phosphorylation at S720 promotes TBX3 protein stability, nuclear localization, transcriptional repression of E-cadherin, and its role in cell migration and invasion. Our results identify a novel signalling and transcriptional network linking AKT3, TBX3 and E-cadherin during melanoma migration and invasion and reveals TBX3 as a potential target for anti-metastatic therapeutics. |
format | Online Article Text |
id | pubmed-4359334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-43593342015-03-26 The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis Peres, Jade Mowla, Shaheen Prince, Sharon Oncotarget Research Paper The AKT3 signalling pathway plays a critical role in melanoma formation and invasion and components of this signalling cascade are therefore attractive targets for the treatment of malignant melanoma. Recent evidence show that the embryonically important TBX3 transcription factor is upregulated in a subset of melanomas and plays a key role in promoting melanoma formation and invasion, in part by repressing the cell adhesion molecule E-cadherin. We have identified TBX3 as a key substrate of AKT3 in melanomagenesis. Briefly, using site-directed mutagenesis and in vitro kinase assays, we have identified the AKT3 target site at serine residue 720 in the TBX3 protein and show that this site is phosphorylated in vivo. Importantly, we show by western blotting, immunofluorescence, reporter, migration and invasion assays that the phosphorylation at S720 promotes TBX3 protein stability, nuclear localization, transcriptional repression of E-cadherin, and its role in cell migration and invasion. Our results identify a novel signalling and transcriptional network linking AKT3, TBX3 and E-cadherin during melanoma migration and invasion and reveals TBX3 as a potential target for anti-metastatic therapeutics. Impact Journals LLC 2014-12-16 /pmc/articles/PMC4359334/ /pubmed/25595898 Text en Copyright: © 2015 Peres et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Peres, Jade Mowla, Shaheen Prince, Sharon The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis |
title | The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis |
title_full | The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis |
title_fullStr | The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis |
title_full_unstemmed | The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis |
title_short | The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis |
title_sort | t-box transcription factor, tbx3, is a key substrate of akt3 in melanomagenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359334/ https://www.ncbi.nlm.nih.gov/pubmed/25595898 |
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