PMID- 25738636 OWN - NLM STAT- MEDLINE DCOM- 20151215 LR - 20201209 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 33 IP - 5 DP - 2015 May TI - Effects of the knockdown of death-associated protein 3 expression on cell adhesion, growth and migration in breast cancer cells. PG - 2575-82 LID - 10.3892/or.2015.3825 [doi] AB - 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-beta 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. FAU - Wazir, Umar AU - Wazir U AD - The London Breast Institute, Princess Grace Hospital, London, UK. FAU - Sanders, Andrew J AU - Sanders AJ AD - Cardiff University-Peking University Cancer Institute (CUPUCI), Cardiff University School of Medicine, Cardiff University, Cardiff, Wales, UK. FAU - Wazir, Ahmad M A AU - Wazir AM AD - Peshawar Medical College, Peshawar, Pakistan. FAU - Ye, Lin AU - Ye L AD - Cardiff University-Peking University Cancer Institute (CUPUCI), Cardiff University School of Medicine, Cardiff University, Cardiff, Wales, UK. FAU - Jiang, Wen G AU - Jiang WG AD - Cardiff University-Peking University Cancer Institute (CUPUCI), Cardiff University School of Medicine, Cardiff University, Cardiff, Wales, UK. FAU - Ster, Irina C AU - Ster IC AD - Department of Breast Surgery, St. George's Hospital and Medical School, University of London, London, UK. FAU - Sharma, Anup K AU - Sharma AK AD - Department of Breast Surgery, St. George's Hospital and Medical School, University of London, London, UK. FAU - Mokbel, Kefah AU - Mokbel K AD - The London Breast Institute, Princess Grace Hospital, London, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150302 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (CDKN1A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (DAP3 protein, human) RN - 0 (DELE1 protein, human) RN - 0 (MAVS protein, human) RN - 0 (Mitochondrial Proteins) RN - 0 (RNA-Binding Proteins) RN - 0 (Ribosomal Proteins) RN - 136601-57-5 (Cyclin D1) RN - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases) RN - EC 3.4.22.- (Caspase 8) RN - EC 3.4.22.- (Caspase 9) SB - IM MH - Adaptor Proteins, Signal Transducing/genetics MH - Apoptosis/genetics MH - Apoptosis Regulatory Proteins/*genetics MH - Breast Neoplasms/*genetics/pathology MH - Caspase 8/genetics MH - Caspase 9/genetics MH - Cell Adhesion/*genetics MH - Cell Line, Tumor MH - Cell Movement/*genetics MH - Cell Proliferation/*genetics MH - Cyclin D1/genetics MH - Cyclin-Dependent Kinase Inhibitor p21/genetics MH - Female MH - Focal Adhesion Protein-Tyrosine Kinases/genetics MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - MCF-7 Cells MH - Mitochondrial Proteins/genetics MH - Neoplasm Invasiveness/genetics/pathology MH - RNA-Binding Proteins MH - Ribosomal Proteins/*genetics MH - Signal Transduction/genetics EDAT- 2015/03/05 06:00 MHDA- 2015/12/17 06:00 CRDT- 2015/03/05 06:00 PHST- 2014/12/30 00:00 [received] PHST- 2015/02/04 00:00 [accepted] PHST- 2015/03/05 06:00 [entrez] PHST- 2015/03/05 06:00 [pubmed] PHST- 2015/12/17 06:00 [medline] AID - 10.3892/or.2015.3825 [doi] PST - ppublish SO - Oncol Rep. 2015 May;33(5):2575-82. doi: 10.3892/or.2015.3825. Epub 2015 Mar 2.