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

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    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 languageEnglish
    Article number18605
    JournalScientific Reports
    Volume10
    Issue number1
    DOIs
    Publication statusPublished - 29 Oct 2020

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