The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression
Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription fact...
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Impact Journals LLC
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914345/ |
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pubmed-49143452016-07-11 The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression Shepherd, Jonathan H. Uray, Ivan P. Mazumdar, Abhijit Tsimelzon, Anna Savage, Michelle Hilsenbeck, Susan G. Brown, Powel H. Research Paper Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer. Impact Journals LLC 2016-02-17 /pmc/articles/PMC4914345/ /pubmed/26894864 http://dx.doi.org/10.18632/oncotarget.7437 Text en Copyright: © 2016 Shepherd et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Shepherd, Jonathan H. Uray, Ivan P. Mazumdar, Abhijit Tsimelzon, Anna Savage, Michelle Hilsenbeck, Susan G. Brown, Powel H. |
| spellingShingle |
Shepherd, Jonathan H. Uray, Ivan P. Mazumdar, Abhijit Tsimelzon, Anna Savage, Michelle Hilsenbeck, Susan G. Brown, Powel H. The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression |
| author_facet |
Shepherd, Jonathan H. Uray, Ivan P. Mazumdar, Abhijit Tsimelzon, Anna Savage, Michelle Hilsenbeck, Susan G. Brown, Powel H. |
| author_sort |
Shepherd, Jonathan H. |
| title |
The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression |
| title_short |
The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression |
| title_full |
The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression |
| title_fullStr |
The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression |
| title_full_unstemmed |
The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression |
| title_sort |
sox11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression |
| description |
Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer. |
| publisher |
Impact Journals LLC |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914345/ |
| _version_ |
1613597207065264128 |