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Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines
Heat shock factor 1 (HSF1) has long been recognized as the master transcription factor that regulates heat shock proteins (HSPs). More recently HSF1 has been associated with a broader role in regulating response to a variety of cellular stresses beyond heat-shock. We previously found that high HSF...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536274/ https://www.ncbi.nlm.nih.gov/pubmed/26223813 http://dx.doi.org/10.1007/s10549-015-3521-1 |
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author | Wang, Bin Lee, Chung-Wei Witt, Abigail Thakkar, Ankita Ince, Tan A. |
author_facet | Wang, Bin Lee, Chung-Wei Witt, Abigail Thakkar, Ankita Ince, Tan A. |
author_sort | Wang, Bin |
collection | PubMed |
description | Heat shock factor 1 (HSF1) has long been recognized as the master transcription factor that regulates heat shock proteins (HSPs). More recently HSF1 has been associated with a broader role in regulating response to a variety of cellular stresses beyond heat-shock. We previously found that high HSF1 expression is associated with poor outcome in lung, breast and colon cancers. Importantly, however, the HSF1 signature correlated with poor outcome in these studies was not related to the heat shock response, which suggested that tumor outcome associated with high HSF expression may be due to processes other than stress response. Hence, we explored the question whether high HSF1 expression might be associated with the cancer stem cell (CSC) phenotype. To do so, we examined the association of HSF1 with CSC phenotype by FACS and immunofluorescence. In addition, we evaluated the effects of HSF1 over-expression and knock-down on sphere formation and CSC marker expression in breast cancer cell lines. Here, we report results demonstrating that high HSF1 not only correlates with CSC marker expression, but inducible HSF1 over-expression augments and HSF1 knock-down inhibits CSC phenotype. Furthermore, HSF1 expression confers resistance to chemotherapeutic drugs and increases CSC frequency. In conclusion, our study indicates that one of the potential HSP-independent HSF1 driven mechanisms that may contribute to poor outcome in human tumors involves regulation of the CSC phenotype. Hence, therapeutic inhibition of HSF1 may be one route to target CSCs in human tumors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-015-3521-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4536274 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-45362742015-08-20 Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines Wang, Bin Lee, Chung-Wei Witt, Abigail Thakkar, Ankita Ince, Tan A. Breast Cancer Res Treat Preclinical Study Heat shock factor 1 (HSF1) has long been recognized as the master transcription factor that regulates heat shock proteins (HSPs). More recently HSF1 has been associated with a broader role in regulating response to a variety of cellular stresses beyond heat-shock. We previously found that high HSF1 expression is associated with poor outcome in lung, breast and colon cancers. Importantly, however, the HSF1 signature correlated with poor outcome in these studies was not related to the heat shock response, which suggested that tumor outcome associated with high HSF expression may be due to processes other than stress response. Hence, we explored the question whether high HSF1 expression might be associated with the cancer stem cell (CSC) phenotype. To do so, we examined the association of HSF1 with CSC phenotype by FACS and immunofluorescence. In addition, we evaluated the effects of HSF1 over-expression and knock-down on sphere formation and CSC marker expression in breast cancer cell lines. Here, we report results demonstrating that high HSF1 not only correlates with CSC marker expression, but inducible HSF1 over-expression augments and HSF1 knock-down inhibits CSC phenotype. Furthermore, HSF1 expression confers resistance to chemotherapeutic drugs and increases CSC frequency. In conclusion, our study indicates that one of the potential HSP-independent HSF1 driven mechanisms that may contribute to poor outcome in human tumors involves regulation of the CSC phenotype. Hence, therapeutic inhibition of HSF1 may be one route to target CSCs in human tumors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-015-3521-1) contains supplementary material, which is available to authorized users. Springer US 2015-07-30 2015 /pmc/articles/PMC4536274/ /pubmed/26223813 http://dx.doi.org/10.1007/s10549-015-3521-1 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided 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. |
spellingShingle | Preclinical Study Wang, Bin Lee, Chung-Wei Witt, Abigail Thakkar, Ankita Ince, Tan A. Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines |
title | Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines |
title_full | Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines |
title_fullStr | Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines |
title_full_unstemmed | Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines |
title_short | Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines |
title_sort | heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines |
topic | Preclinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536274/ https://www.ncbi.nlm.nih.gov/pubmed/26223813 http://dx.doi.org/10.1007/s10549-015-3521-1 |
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