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SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer.
- Source :
-
Scientific reports [Sci Rep] 2020 Oct 29; Vol. 10 (1), pp. 18605. Date of Electronic Publication: 2020 Oct 29. - Publication Year :
- 2020
-
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.
- Subjects :
- A549 Cells
Apoptosis drug effects
Apoptosis physiology
Carcinoma, Non-Small-Cell Lung drug therapy
Cell Line, Tumor
Cell Proliferation drug effects
Cell Proliferation physiology
Cisplatin pharmacology
Gene Expression Regulation, Neoplastic drug effects
Gene Expression Regulation, Neoplastic physiology
Humans
Lung Neoplasms drug therapy
Prognosis
RNA, Messenger metabolism
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung physiopathology
Lung Neoplasms metabolism
Lung Neoplasms pathology
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33122723
- Full Text :
- https://doi.org/10.1038/s41598-020-75625-1