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HSF1 REGULATION OF β-CATENIN IN MAMMARY CANCER CELLS THROUGH CONTROL OF HUR / ELAVL1 EXPRESSION

There is now compelling evidence to indicate a place for heat shock factor 1 (HSF1) in mammary carcinogenesis, tumor progression and metastasis. Here we have investigated a role for HSF1 in regulating the expression of the stem cell renewal factor β-catenin in immortalized human mammary epithelial a...

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Autores principales: Chou, Shiuh-Dih, Murshid, Ayesha, Eguchi, Takanori, Gong, Jianlin, Calderwood, Stuart K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275421/
https://www.ncbi.nlm.nih.gov/pubmed/24954509
http://dx.doi.org/10.1038/onc.2014.177
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author Chou, Shiuh-Dih
Murshid, Ayesha
Eguchi, Takanori
Gong, Jianlin
Calderwood, Stuart K
author_facet Chou, Shiuh-Dih
Murshid, Ayesha
Eguchi, Takanori
Gong, Jianlin
Calderwood, Stuart K
author_sort Chou, Shiuh-Dih
collection PubMed
description There is now compelling evidence to indicate a place for heat shock factor 1 (HSF1) in mammary carcinogenesis, tumor progression and metastasis. Here we have investigated a role for HSF1 in regulating the expression of the stem cell renewal factor β-catenin in immortalized human mammary epithelial and carcinoma cells. We found HSF1 to be involved in regulating the translation of β–catenin, by investigating effects of gain and loss of HSF1 on this protein. Interestingly, although HSF1 is a potent transcription factor, it was not directly involved in regulating levels of β-catenin mRNA. Instead, our data suggest a complex role in translational regulation. HSF1 was shown to regulate levels of the RNA binding protein HuR that controlled β-catenin translation. An extra complexity was added to this scenario when it was shown that the long non-coding RNA molecule lincRNA-p21, known to be involved in β-catenin mRNA (CTNNB1) translational regulation, was controlled by HSF1 repression. We have shown previously that HSF1 was positively regulated through phosphorylation by mTOR kinase on a key residue, serine 326 essential for transcriptional activity. In this study we found that mTOR knockdown not only decreased HSF1-S326 phosphorylation in mammary cells, but also decreased β-catenin expression through a mechanism requiring HuR. Our data point to a complex role for HSF1 in the regulation of HuR and β-catenin expression that may be significant in mammary carcinogenesis.
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spelling pubmed-42754212015-10-23 HSF1 REGULATION OF β-CATENIN IN MAMMARY CANCER CELLS THROUGH CONTROL OF HUR / ELAVL1 EXPRESSION Chou, Shiuh-Dih Murshid, Ayesha Eguchi, Takanori Gong, Jianlin Calderwood, Stuart K Oncogene Article There is now compelling evidence to indicate a place for heat shock factor 1 (HSF1) in mammary carcinogenesis, tumor progression and metastasis. Here we have investigated a role for HSF1 in regulating the expression of the stem cell renewal factor β-catenin in immortalized human mammary epithelial and carcinoma cells. We found HSF1 to be involved in regulating the translation of β–catenin, by investigating effects of gain and loss of HSF1 on this protein. Interestingly, although HSF1 is a potent transcription factor, it was not directly involved in regulating levels of β-catenin mRNA. Instead, our data suggest a complex role in translational regulation. HSF1 was shown to regulate levels of the RNA binding protein HuR that controlled β-catenin translation. An extra complexity was added to this scenario when it was shown that the long non-coding RNA molecule lincRNA-p21, known to be involved in β-catenin mRNA (CTNNB1) translational regulation, was controlled by HSF1 repression. We have shown previously that HSF1 was positively regulated through phosphorylation by mTOR kinase on a key residue, serine 326 essential for transcriptional activity. In this study we found that mTOR knockdown not only decreased HSF1-S326 phosphorylation in mammary cells, but also decreased β-catenin expression through a mechanism requiring HuR. Our data point to a complex role for HSF1 in the regulation of HuR and β-catenin expression that may be significant in mammary carcinogenesis. 2014-06-23 2015-04-23 /pmc/articles/PMC4275421/ /pubmed/24954509 http://dx.doi.org/10.1038/onc.2014.177 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Chou, Shiuh-Dih
Murshid, Ayesha
Eguchi, Takanori
Gong, Jianlin
Calderwood, Stuart K
HSF1 REGULATION OF β-CATENIN IN MAMMARY CANCER CELLS THROUGH CONTROL OF HUR / ELAVL1 EXPRESSION
title HSF1 REGULATION OF β-CATENIN IN MAMMARY CANCER CELLS THROUGH CONTROL OF HUR / ELAVL1 EXPRESSION
title_full HSF1 REGULATION OF β-CATENIN IN MAMMARY CANCER CELLS THROUGH CONTROL OF HUR / ELAVL1 EXPRESSION
title_fullStr HSF1 REGULATION OF β-CATENIN IN MAMMARY CANCER CELLS THROUGH CONTROL OF HUR / ELAVL1 EXPRESSION
title_full_unstemmed HSF1 REGULATION OF β-CATENIN IN MAMMARY CANCER CELLS THROUGH CONTROL OF HUR / ELAVL1 EXPRESSION
title_short HSF1 REGULATION OF β-CATENIN IN MAMMARY CANCER CELLS THROUGH CONTROL OF HUR / ELAVL1 EXPRESSION
title_sort hsf1 regulation of β-catenin in mammary cancer cells through control of hur / elavl1 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275421/
https://www.ncbi.nlm.nih.gov/pubmed/24954509
http://dx.doi.org/10.1038/onc.2014.177
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