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Oncol Rep. 2015 May;33(5):2575-82. doi: 10.3892/or.2015.3825. Epub 2015 Mar 2.

Effects of the knockdown of death-associated protein 3 expression on cell adhesion, growth and migration in breast cancer cells.

Author information

1
The London Breast Institute, Princess Grace Hospital, London, UK.
2
Cardiff University-Peking University Cancer InstituteĀ (CUPUCI), Cardiff University School of Medicine, Cardiff University, Cardiff, Wales, UK.
3
Peshawar Medical College, Peshawar, Pakistan.
4
Department of Breast Surgery, St. George's Hospital and Medical School, University of London, London, UK.

Abstract

The death-associated protein 3 (DAP3) is a highly conserved phosphoprotein involved in the regulation of autophagy. A previous clinical study by our group suggested an association between low DAP3 expression and clinicopathological parameters of human breast cancer. In the present study, we intended to determine the role of DAP3 in cancer cell behaviour in the context of human breast cancer. We developed knockdown sub-lines of MCF7 and MDA-MB-231, and performed growth, adhesion, invasion assays and electric cell-substrate impedance sensing (ECIS) studies of post-wound migration of the cells. In addition, we studied the mRNA expression of caspase 8 and 9, death ligand signal enhancer (DELE), IFN-Ī² promoter stimulator 1 (IPS1), cyclin D1 and p21 in the control and knockdown sub-lines. The knockdown sub-lines of MCF7 and MDA-MB-231 had significantly increased adhesion and decreased growth when compared to the controls. Furthermore, invasion and migration were significantly increased in the MDA-MB-231DAP3kd cells vs. the controls. The expression of caspase 9 and IPS1, known components of the apoptosis pathway, were significantly reduced in the MCF7DAP3kd cells (p=0.05 and p=0.003, respectively). We conclude that DAP3 silencing contributes to breast carcinogenesis by increasing cell adhesion, migration and invasion. It is possible that this may be due to the activity of focal adhesion kinase further downstream of the anoikis pathway. Further research in this direction would be beneficial in increasing our understanding of the mechanisms underlying human breast cancer.

PMID:
25738636
DOI:
10.3892/or.2015.3825
[Indexed for MEDLINE]

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