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SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer

SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor protein that has roles in key cellular processes including apoptosis and cellular proliferation. As these cellular processes are frequently disrupted in human tumours and little is known about the role of SASH1 in the pathogenesis...

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Autores principales: Burgess, Joshua T., Bolderson, Emma, Adams, Mark N., Duijf, Pascal H. G., Zhang, Shu-Dong, Gray, Steven G., Wright, Gavin, Richard, Derek J., O’Byrne, Kenneth J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596716/
https://www.ncbi.nlm.nih.gov/pubmed/33122723
http://dx.doi.org/10.1038/s41598-020-75625-1
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author Burgess, Joshua T.
Bolderson, Emma
Adams, Mark N.
Duijf, Pascal H. G.
Zhang, Shu-Dong
Gray, Steven G.
Wright, Gavin
Richard, Derek J.
O’Byrne, Kenneth J.
author_facet Burgess, Joshua T.
Bolderson, Emma
Adams, Mark N.
Duijf, Pascal H. G.
Zhang, Shu-Dong
Gray, Steven G.
Wright, Gavin
Richard, Derek J.
O’Byrne, Kenneth J.
author_sort Burgess, Joshua T.
collection PubMed
description SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor protein that has roles in key cellular processes including apoptosis and cellular proliferation. As these cellular processes are frequently disrupted in human tumours and little is known about the role of SASH1 in the pathogenesis of the disease, we analysed the prognostic value of SASH1 in non-small cell lung cancers using publicly available datasets. Here, we show that low SASH1 mRNA expression is associated with poor survival in adenocarcinoma. Supporting this, modulation of SASH1 levels in a panel of lung cancer cell lines mediated changes in cellular proliferation and sensitivity to cisplatin. The treatment of lung cancer cells with chloropyramine, a compound that increases SASH1 protein concentrations, reduced cellular proliferation and increased sensitivity to cisplatin in a SASH1-dependent manner. In summary, compounds that increase SASH1 protein levels could represent a novel approach to treat NSCLC and warrant further study.
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spelling pubmed-75967162020-11-03 SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer Burgess, Joshua T. Bolderson, Emma Adams, Mark N. Duijf, Pascal H. G. Zhang, Shu-Dong Gray, Steven G. Wright, Gavin Richard, Derek J. O’Byrne, Kenneth J. Sci Rep Article SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor protein that has roles in key cellular processes including apoptosis and cellular proliferation. As these cellular processes are frequently disrupted in human tumours and little is known about the role of SASH1 in the pathogenesis of the disease, we analysed the prognostic value of SASH1 in non-small cell lung cancers using publicly available datasets. Here, we show that low SASH1 mRNA expression is associated with poor survival in adenocarcinoma. Supporting this, modulation of SASH1 levels in a panel of lung cancer cell lines mediated changes in cellular proliferation and sensitivity to cisplatin. The treatment of lung cancer cells with chloropyramine, a compound that increases SASH1 protein concentrations, reduced cellular proliferation and increased sensitivity to cisplatin in a SASH1-dependent manner. In summary, compounds that increase SASH1 protein levels could represent a novel approach to treat NSCLC and warrant further study. Nature Publishing Group UK 2020-10-29 /pmc/articles/PMC7596716/ /pubmed/33122723 http://dx.doi.org/10.1038/s41598-020-75625-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Burgess, Joshua T.
Bolderson, Emma
Adams, Mark N.
Duijf, Pascal H. G.
Zhang, Shu-Dong
Gray, Steven G.
Wright, Gavin
Richard, Derek J.
O’Byrne, Kenneth J.
SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer
title SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer
title_full SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer
title_fullStr SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer
title_full_unstemmed SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer
title_short SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer
title_sort sash1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596716/
https://www.ncbi.nlm.nih.gov/pubmed/33122723
http://dx.doi.org/10.1038/s41598-020-75625-1
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