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The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1
Aberrant re-activation of transcription factors occurs frequently in cancer. Recently, we found the basic helix-loop-helix transcription factors DEC1 and DEC2 significantly up-regulated in a model of highly aggressive thyroid cancer, raising the hypothesis that these factors might be part of the pro...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115386/ https://www.ncbi.nlm.nih.gov/pubmed/30158530 http://dx.doi.org/10.1038/s41419-018-0933-y |
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author | Gallo, Cristina Fragliasso, Valentina Donati, Benedetta Torricelli, Federica Tameni, Annalisa Piana, Simonetta Ciarrocchi, Alessia |
author_facet | Gallo, Cristina Fragliasso, Valentina Donati, Benedetta Torricelli, Federica Tameni, Annalisa Piana, Simonetta Ciarrocchi, Alessia |
author_sort | Gallo, Cristina |
collection | PubMed |
description | Aberrant re-activation of transcription factors occurs frequently in cancer. Recently, we found the basic helix-loop-helix transcription factors DEC1 and DEC2 significantly up-regulated in a model of highly aggressive thyroid cancer, raising the hypothesis that these factors might be part of the program driving progression of these tumors. Here, we investigated for the first time the function of DEC1 and DEC2 in thyroid cancer. Using both gain- and loss-of-function approaches, we showed that DEC1 more than DEC2 sustains progression of thyroid cancer by promoting cell growth and invasiveness. We demonstrated that DEC1 controls NOTCH1 expression and that the interplay with the NOTCH pathway is relevant for DEC1 function in thyroid cancer. We confirmed this observation in vivo showing that DEC1 expression is a specific feature of tumor cells, that this transcription factor is significantly over-expressed in all major thyroid cancer histotypes and that its expression correlated with NOTCH1 in these tumors. Finally, we performed RNA-sequencing to define the DEC1-associated gene expression profile in thyroid cancer cells and we discovered that DEC1 drives the expression of many cell cycle-related genes, uncovering a potential new function for this transcription factor in cancer. |
format | Online Article Text |
id | pubmed-6115386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61153862018-08-30 The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1 Gallo, Cristina Fragliasso, Valentina Donati, Benedetta Torricelli, Federica Tameni, Annalisa Piana, Simonetta Ciarrocchi, Alessia Cell Death Dis Article Aberrant re-activation of transcription factors occurs frequently in cancer. Recently, we found the basic helix-loop-helix transcription factors DEC1 and DEC2 significantly up-regulated in a model of highly aggressive thyroid cancer, raising the hypothesis that these factors might be part of the program driving progression of these tumors. Here, we investigated for the first time the function of DEC1 and DEC2 in thyroid cancer. Using both gain- and loss-of-function approaches, we showed that DEC1 more than DEC2 sustains progression of thyroid cancer by promoting cell growth and invasiveness. We demonstrated that DEC1 controls NOTCH1 expression and that the interplay with the NOTCH pathway is relevant for DEC1 function in thyroid cancer. We confirmed this observation in vivo showing that DEC1 expression is a specific feature of tumor cells, that this transcription factor is significantly over-expressed in all major thyroid cancer histotypes and that its expression correlated with NOTCH1 in these tumors. Finally, we performed RNA-sequencing to define the DEC1-associated gene expression profile in thyroid cancer cells and we discovered that DEC1 drives the expression of many cell cycle-related genes, uncovering a potential new function for this transcription factor in cancer. Nature Publishing Group UK 2018-08-29 /pmc/articles/PMC6115386/ /pubmed/30158530 http://dx.doi.org/10.1038/s41419-018-0933-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Gallo, Cristina Fragliasso, Valentina Donati, Benedetta Torricelli, Federica Tameni, Annalisa Piana, Simonetta Ciarrocchi, Alessia The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1 |
title | The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1 |
title_full | The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1 |
title_fullStr | The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1 |
title_full_unstemmed | The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1 |
title_short | The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1 |
title_sort | bhlh transcription factor dec1 promotes thyroid cancer aggressiveness by the interplay with notch1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115386/ https://www.ncbi.nlm.nih.gov/pubmed/30158530 http://dx.doi.org/10.1038/s41419-018-0933-y |
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