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HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ
Transcriptional coactivator with PDZ-binding motif (TAZ) is a downstream transcriptional regulator of the Hippo pathway that controls cell growth and differentiation. The aberrant activation of TAZ correlates with a poor prognosis in human cancers, such as breast and colon cancers. We previously dem...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412369/ https://www.ncbi.nlm.nih.gov/pubmed/36015162 http://dx.doi.org/10.3390/ph15081015 |
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author | Miyajima, Chiharu Hayakawa, Yurika Inoue, Yasumichi Nagasaka, Mai Hayashi, Hidetoshi |
author_facet | Miyajima, Chiharu Hayakawa, Yurika Inoue, Yasumichi Nagasaka, Mai Hayashi, Hidetoshi |
author_sort | Miyajima, Chiharu |
collection | PubMed |
description | Transcriptional coactivator with PDZ-binding motif (TAZ) is a downstream transcriptional regulator of the Hippo pathway that controls cell growth and differentiation. The aberrant activation of TAZ correlates with a poor prognosis in human cancers, such as breast and colon cancers. We previously demonstrated that TAZ inhibited the tumor suppressor functions of p53 and enhanced cell proliferation. Statins, which are used to treat dyslipidemia, have been reported to suppress the activity of TAZ and exert anti-tumor effects. In the present study, we focused on the regulation of p53 functions by TAZ and investigated whether statins modulate these functions via TAZ. The results obtained suggest that statins, such as simvastatin and fluvastatin, activated the transcriptional function of p53 by suppressing TAZ protein expression. Furthermore, co-treatment with simvastatin and anti-tumor agents that cooperatively activate p53 suppressed cancer cell survival. These results indicate a useful mechanism by which statins enhance the effects of anti-tumor agents through the activation of p53 and may represent a novel approach to cancer therapy. |
format | Online Article Text |
id | pubmed-9412369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94123692022-08-27 HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ Miyajima, Chiharu Hayakawa, Yurika Inoue, Yasumichi Nagasaka, Mai Hayashi, Hidetoshi Pharmaceuticals (Basel) Article Transcriptional coactivator with PDZ-binding motif (TAZ) is a downstream transcriptional regulator of the Hippo pathway that controls cell growth and differentiation. The aberrant activation of TAZ correlates with a poor prognosis in human cancers, such as breast and colon cancers. We previously demonstrated that TAZ inhibited the tumor suppressor functions of p53 and enhanced cell proliferation. Statins, which are used to treat dyslipidemia, have been reported to suppress the activity of TAZ and exert anti-tumor effects. In the present study, we focused on the regulation of p53 functions by TAZ and investigated whether statins modulate these functions via TAZ. The results obtained suggest that statins, such as simvastatin and fluvastatin, activated the transcriptional function of p53 by suppressing TAZ protein expression. Furthermore, co-treatment with simvastatin and anti-tumor agents that cooperatively activate p53 suppressed cancer cell survival. These results indicate a useful mechanism by which statins enhance the effects of anti-tumor agents through the activation of p53 and may represent a novel approach to cancer therapy. MDPI 2022-08-17 /pmc/articles/PMC9412369/ /pubmed/36015162 http://dx.doi.org/10.3390/ph15081015 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Miyajima, Chiharu Hayakawa, Yurika Inoue, Yasumichi Nagasaka, Mai Hayashi, Hidetoshi HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ |
title | HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ |
title_full | HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ |
title_fullStr | HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ |
title_full_unstemmed | HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ |
title_short | HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ |
title_sort | hmg-coa reductase inhibitor statins activate the transcriptional activity of p53 by regulating the expression of taz |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412369/ https://www.ncbi.nlm.nih.gov/pubmed/36015162 http://dx.doi.org/10.3390/ph15081015 |
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