Steinmann, Sara and Kunze, Philipp and Hampel, Chuanpit and Eckstein, Markus and Bramsen, Jesper Bertram and Muenzner, Julienne K. and Carle, Birgitta and Ndreshkjana, Benardina and Kemenes, Stephan and Gasparini, Pierluigi and Friedrich, Oliver and Andersen, Claus and Geppert, Carol and Wang, Shengbao and Eyupoglu, Ilker and Baeuerle, Tobias and Hartmann, Arndt and Schneider-Stock, Regine (2019) DAPK1 loss triggers tumor invasion in colorectal tumor cells. CELL DEATH & DISEASE, 10: 895. ISSN 2041-4889,
Full text not available from this repository. (Request a copy)Abstract
Colorectal cancer (CRC) is one of the leading cancer-related causes of death worldwide. Despite the improvement of surgical and chemotherapeutic treatments, as of yet, the disease has not been overcome due to metastasis to distant organs. Hence, it is of great relevance to understand the mechanisms responsible for metastasis initiation and progression and to identify novel metastatic markers for a higher chance of preventing the metastatic disease. The Death-associated protein kinase 1 (DAPK1), recently, has been shown to be a potential candidate for regulating metastasis in CRC. Hence, the aim of the study was to investigate the impact of DAPK1 protein on CRC aggressiveness. Using CRISPR/Cas9 technology, we generated DAPK1-deficient HCT116 monoclonal cell lines and characterized their knockout phenotype in vitro and in vivo. We show that loss of DAPK1 implemented changes in growth pattern and enhanced tumor budding in vivo in the chorioallantoic membrane (CAM) model. Further, we observed more tumor cell dissemination into chicken embryo organs and increased invasion capacity using rat brain 3D in vitro model. The novel identified DAPK1-loss gene expression signature showed a stroma typical pattern and was associated with a gained ability for remodeling the extracellular matrix. Finally, we suggest the DAPK1-ERK1 signaling axis being involved in metastatic progression of CRC. Our results highlight DAPK1 as an anti-metastatic player in CRC and suggest DAPK1 as a potential predictive biomarker for this cancer type.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERCELLULAR-ADHESION MOLECULE-1; PROTEIN-KINASE EXPRESSION; SET ENRICHMENT ANALYSIS; CANCER METASTASIS; TNF-ALPHA; DEATH; METHYLATION; APOPTOSIS; PROMOTES; IDENTIFICATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Unfallchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2020 12:09 |
| Last Modified: | 23 Mar 2020 12:09 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25799 |
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