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

Joshua T. Burgess; Emma Bolderson; Mark N. Adams; Pascal H.G. Duijf; Shu Dong Zhang; Steven G. Gray; Gavin Wright; Derek J. Richard; Kenneth J. O’Byrne

doi:10.1038/s41598-020-75625-1

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

Joshua T. Burgess, Emma Bolderson, Mark N. Adams, Pascal H.G. Duijf, Shu Dong Zhang, Steven G. Gray, Gavin Wright, Derek J. Richard, Kenneth J. O’Byrne

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

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.

Original language	English
Article number	18605
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-75625-1
Publication status	Published (in print/issue) - 29 Oct 2020

Bibliographical note

Funding Information:
This work was supported by a Grant from the Princess Alexandra Hospital Research Foundation, National Breast Cancer Foundation and a Queensland Senior Clinical Research Fellowship. JB is supported by an Advance Queensland Early-career Research Fellowship. EB is supported by an Advance Queensland Senior Research Fellowship. MNA is supported by a NHMRC Early Career Biomedical Fellowship (1091589) and is an IASLC Foundation Awardee supported by the International Association for the Study of Lung Cancer Foundation.

Publisher Copyright:
© 2020, The Author(s).

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

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

abstract = "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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note = "Funding Information: This work was supported by a Grant from the Princess Alexandra Hospital Research Foundation, National Breast Cancer Foundation and a Queensland Senior Clinical Research Fellowship. JB is supported by an Advance Queensland Early-career Research Fellowship. EB is supported by an Advance Queensland Senior Research Fellowship. MNA is supported by a NHMRC Early Career Biomedical Fellowship (1091589) and is an IASLC Foundation Awardee supported by the International Association for the Study of Lung Cancer Foundation. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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doi = "10.1038/s41598-020-75625-1",

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AU - Bolderson, Emma

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AU - Gray, Steven G.

AU - Wright, Gavin

AU - Richard, Derek J.

AU - O’Byrne, Kenneth J.

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

Abstract

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