Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783602173685268480 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7596716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT burgessjoshuat sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer AT boldersonemma sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer AT adamsmarkn sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer AT duijfpascalhg sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer AT zhangshudong sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer AT graysteveng sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer AT wrightgavin sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer AT richardderekj sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer AT obyrnekennethj sash1isaprognosticindicatorandpotentialtherapeutictargetinnonsmallcelllungcancer |