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HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architect...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721465/ https://www.ncbi.nlm.nih.gov/pubmed/31382504 http://dx.doi.org/10.3390/cancers11081105 |
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author | Penzo, Carlotta Arnoldo, Laura Pegoraro, Silvia Petrosino, Sara Ros, Gloria Zanin, Rossella Wiśniewski, Jacek R. Manfioletti, Guidalberto Sgarra, Riccardo |
author_facet | Penzo, Carlotta Arnoldo, Laura Pegoraro, Silvia Petrosino, Sara Ros, Gloria Zanin, Rossella Wiśniewski, Jacek R. Manfioletti, Guidalberto Sgarra, Riccardo |
author_sort | Penzo, Carlotta |
collection | PubMed |
description | Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architectural chromatin transcription factor that alters DNA structure and interacts with transcription factors favouring their landing onto transcription regulatory sequences. Here, we provide evidence of an additional mechanism exploited by HMGA1 to modulate transcription. We demonstrate that, in a triple-negative breast cancer cellular model, HMGA1 sustains the action of epigenetic modifiers and in particular it positively influences both histone H3S10 phosphorylation by ribosomal protein S6 kinase alpha-3 (RSK2) and histone H2BK5 acetylation by CREB-binding protein (CBP). HMGA1, RSK2, and CBP control the expression of a set of genes involved in tumor progression and epithelial to mesenchymal transition. These results suggest that HMGA1 has an effect on the epigenetic status of cancer cells and that it could be exploited as a responsiveness predictor for epigenetic therapies in triple-negative breast cancers. |
format | Online Article Text |
id | pubmed-6721465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67214652019-09-10 HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells Penzo, Carlotta Arnoldo, Laura Pegoraro, Silvia Petrosino, Sara Ros, Gloria Zanin, Rossella Wiśniewski, Jacek R. Manfioletti, Guidalberto Sgarra, Riccardo Cancers (Basel) Article Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architectural chromatin transcription factor that alters DNA structure and interacts with transcription factors favouring their landing onto transcription regulatory sequences. Here, we provide evidence of an additional mechanism exploited by HMGA1 to modulate transcription. We demonstrate that, in a triple-negative breast cancer cellular model, HMGA1 sustains the action of epigenetic modifiers and in particular it positively influences both histone H3S10 phosphorylation by ribosomal protein S6 kinase alpha-3 (RSK2) and histone H2BK5 acetylation by CREB-binding protein (CBP). HMGA1, RSK2, and CBP control the expression of a set of genes involved in tumor progression and epithelial to mesenchymal transition. These results suggest that HMGA1 has an effect on the epigenetic status of cancer cells and that it could be exploited as a responsiveness predictor for epigenetic therapies in triple-negative breast cancers. MDPI 2019-08-02 /pmc/articles/PMC6721465/ /pubmed/31382504 http://dx.doi.org/10.3390/cancers11081105 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Penzo, Carlotta Arnoldo, Laura Pegoraro, Silvia Petrosino, Sara Ros, Gloria Zanin, Rossella Wiśniewski, Jacek R. Manfioletti, Guidalberto Sgarra, Riccardo HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells |
title | HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells |
title_full | HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells |
title_fullStr | HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells |
title_full_unstemmed | HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells |
title_short | HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells |
title_sort | hmga1 modulates gene transcription sustaining a tumor signalling pathway acting on the epigenetic status of triple-negative breast cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721465/ https://www.ncbi.nlm.nih.gov/pubmed/31382504 http://dx.doi.org/10.3390/cancers11081105 |
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