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The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer

Metastatic prostate cancer is treated with androgen ablation therapy but progress to castrate resistant prostate cancer (CRPC). This study aimed to investigate the role of CUX1 in CRPC using clinical samples and in vitro models. CUX1 expression was increased in androgen-independent cells compared to...

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Autores principales: Dorris, Emma R., O’Neill, Amanda, Treacy, Ann, Klocker, Helmut, Teltsh, Omri, Kay, Elaine, Watson, R. William
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061738/
https://www.ncbi.nlm.nih.gov/pubmed/32180898
http://dx.doi.org/10.18632/oncotarget.27494
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author Dorris, Emma R.
O’Neill, Amanda
Treacy, Ann
Klocker, Helmut
Teltsh, Omri
Kay, Elaine
Watson, R. William
author_facet Dorris, Emma R.
O’Neill, Amanda
Treacy, Ann
Klocker, Helmut
Teltsh, Omri
Kay, Elaine
Watson, R. William
author_sort Dorris, Emma R.
collection PubMed
description Metastatic prostate cancer is treated with androgen ablation therapy but progress to castrate resistant prostate cancer (CRPC). This study aimed to investigate the role of CUX1 in CRPC using clinical samples and in vitro models. CUX1 expression was increased in androgen-independent cells compared to androgen-sensitive cells. The multi-isoform nature of CUX1 makes it difficult to assay in tissue microarrays as there is no epitope able to distinguish the many isoforms for immunohistochemistry. Using surrogate markers, we found no differential expression between castrate resistant and local hormone naïve tissue. However, differences have been demonstrated at the transcript level. In androgen-sensitive cells, migration, but not invasion, increased following CUX1 knockdown. Conversely, in androgen-independent cells, invasion was increased. This observed difference in invasion capacity is not E-cadherin mediated, as CUX1 knockdown increases the expression of E-cadherin in both cell lines with no inter-cell line difference. Cells expressed different ratios of p110/p200 isoforms depending on androgen status and cathepsin L was only detectable in androgen-sensitive cells. MMP3 is upregulated in the androgen-independent cells. Rather than a simple presence or absence of CUX1, the relative balance of CUX1 isoforms and their interplay may be a significant factor in the functional role of CUX1 in CRPC.
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spelling pubmed-70617382020-03-16 The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer Dorris, Emma R. O’Neill, Amanda Treacy, Ann Klocker, Helmut Teltsh, Omri Kay, Elaine Watson, R. William Oncotarget Research Paper Metastatic prostate cancer is treated with androgen ablation therapy but progress to castrate resistant prostate cancer (CRPC). This study aimed to investigate the role of CUX1 in CRPC using clinical samples and in vitro models. CUX1 expression was increased in androgen-independent cells compared to androgen-sensitive cells. The multi-isoform nature of CUX1 makes it difficult to assay in tissue microarrays as there is no epitope able to distinguish the many isoforms for immunohistochemistry. Using surrogate markers, we found no differential expression between castrate resistant and local hormone naïve tissue. However, differences have been demonstrated at the transcript level. In androgen-sensitive cells, migration, but not invasion, increased following CUX1 knockdown. Conversely, in androgen-independent cells, invasion was increased. This observed difference in invasion capacity is not E-cadherin mediated, as CUX1 knockdown increases the expression of E-cadherin in both cell lines with no inter-cell line difference. Cells expressed different ratios of p110/p200 isoforms depending on androgen status and cathepsin L was only detectable in androgen-sensitive cells. MMP3 is upregulated in the androgen-independent cells. Rather than a simple presence or absence of CUX1, the relative balance of CUX1 isoforms and their interplay may be a significant factor in the functional role of CUX1 in CRPC. Impact Journals LLC 2020-03-03 /pmc/articles/PMC7061738/ /pubmed/32180898 http://dx.doi.org/10.18632/oncotarget.27494 Text en Copyright: © 2020 Dorris et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Dorris, Emma R.
O’Neill, Amanda
Treacy, Ann
Klocker, Helmut
Teltsh, Omri
Kay, Elaine
Watson, R. William
The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer
title The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer
title_full The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer
title_fullStr The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer
title_full_unstemmed The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer
title_short The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer
title_sort transcription factor cux1 negatively regulates invasion in castrate resistant prostate cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061738/
https://www.ncbi.nlm.nih.gov/pubmed/32180898
http://dx.doi.org/10.18632/oncotarget.27494
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