16P - The overexpression of SASH1 stimulates cell death in lung cancer cells

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Basic Science
Lung and other Thoracic Tumours
Presenter Kenneth O'Byrne
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors K. O'Byrne1, J. Burgess2, E. Bolderson2, M. Adams2, S. Zhang3, D. Richard2
  • 1Translational Research Institute, Princess Alexandra Hospital and Queensland University of Technology, 4102 - Brisbane/AU
  • 2Institute Of Health And Biomedical Innovation, Cancer And Ageing Research Program, Queensland University of Technology, Brisbane/AU
  • 3Center For Cancer Research And Cell Biology, Queen's University Belfast, Belfast/GB

Abstract

Background

SASH1 (SAM and SH3 domain-containing protein 1) is a recently identified gene with tumour suppressor properties with a role in the induction of apoptosis. Previous work has shown that 90% of lung cell lines have a decrease in SASH1 mRNA levels, however little characterisation of SASH1 function in lung cancer has been undertaken.

Methods

We evaluated SASH1 expression in transformed normal and malignant lung cancer cell lines. We also utilised cell based assays to study the effects of altered SASH1 levels on cell survival and proliferation. Identification of novel SASH1 targeting drug was performed through connectivity mapping.

Results

SASH1 protein expression was down regulated in two of the five lung cancer cell lines compared to normal bronchial cells. Prognoscan assessment identified decrease SASH1 mRNA expression lead to a prognostic reduction in patient survival. The depletion of SASH1 in lung cells resulted in a significant increase in cellular proliferation in cancer lung cells. Connectivity mapping predicted the drug Chloropyramine would lead to an increase in SASH1 expression. We demonstrated that Chloropyramine upregulates SASH1 in malignant cell lines. In keeping with this we have demonstrated that Chloropyramine inhibited lung cancer proliferation in vitro. These novel observations support the tumour suppressive role of SASH1 in lung tumourgenesis. Further work is ongoing to understand the function of SASH1 in lung cancer growth.

Conclusions

The upregulation of SASH1, either by chemical agents or gene therapy, is a potential novel approach to the management of lung cancer and other solid tumours.

Clinical trial identification

Legal entity responsible for the study

Queensland University of Technology

Funding

Queensland Health

Disclosure

All authors have declared no conflicts of interest.