C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell Migration
Pancreatic Ductal Adenocarcinoma (PDAC) is among the most aggressive human cancers and occurs globally at an increasing incidence. Metastases are the primary cause of cancer-related death and, in the majority of cases, PDAC is accompanied by metastatic disease at the time of diagnosis, making it a p...
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MDPI AG
2022-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/21/3334 |
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| author | Leonie Hartl Pien A. F. Maarschalkerweerd Joe M. Butler Xue D. Manz Victor L. J. L. Thijssen Maarten F. Bijlsma JanWillem Duitman C. Arnold Spek |
| author_facet | Leonie Hartl Pien A. F. Maarschalkerweerd Joe M. Butler Xue D. Manz Victor L. J. L. Thijssen Maarten F. Bijlsma JanWillem Duitman C. Arnold Spek |
| author_sort | Leonie Hartl |
| collection | DOAJ |
| description | Pancreatic Ductal Adenocarcinoma (PDAC) is among the most aggressive human cancers and occurs globally at an increasing incidence. Metastases are the primary cause of cancer-related death and, in the majority of cases, PDAC is accompanied by metastatic disease at the time of diagnosis, making it a particularly lethal cancer. Regrettably, to date, no curative treatment has been developed for patients with metastatic disease, resulting in a 5-year survival rate of only 11%. We previously found that the protein expression of the transcription factor CCAAT/Enhancer-Binding Protein Delta (C/EBPδ) negatively correlates with lymph node involvement in PDAC patients. To better comprehend the etiology of metastatic PDAC, we explored the role of C/EBPδ at different steps of the metastatic cascade, using established in vitro models. We found that C/EBPδ has a major impact on cell motility, an important prerequisite for tumor cells to leave the primary tumor and to reach distant sites. Our data suggest that C/EBPδ induces downstream pathways that modulate actin cytoskeleton dynamics to reduce cell migration and to induce a more epithelial-like cellular phenotype. Understanding the mechanisms dictating epithelial and mesenchymal features holds great promise for improving the treatment of PDAC. |
| first_indexed | 2024-03-09T19:11:41Z |
| format | Article |
| id | doaj.art-c40525e5847b4102add33b8dc3094fbd |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T19:11:41Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c40525e5847b4102add33b8dc3094fbd2023-11-24T04:07:04ZengMDPI AGCells2073-44092022-10-011121333410.3390/cells11213334C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell MigrationLeonie Hartl0Pien A. F. Maarschalkerweerd1Joe M. Butler2Xue D. Manz3Victor L. J. L. Thijssen4Maarten F. Bijlsma5JanWillem Duitman6C. Arnold Spek7Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Pulmonary Medicine, Amsterdam UMC Location VU University Medical Center, 1081 HV Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsPancreatic Ductal Adenocarcinoma (PDAC) is among the most aggressive human cancers and occurs globally at an increasing incidence. Metastases are the primary cause of cancer-related death and, in the majority of cases, PDAC is accompanied by metastatic disease at the time of diagnosis, making it a particularly lethal cancer. Regrettably, to date, no curative treatment has been developed for patients with metastatic disease, resulting in a 5-year survival rate of only 11%. We previously found that the protein expression of the transcription factor CCAAT/Enhancer-Binding Protein Delta (C/EBPδ) negatively correlates with lymph node involvement in PDAC patients. To better comprehend the etiology of metastatic PDAC, we explored the role of C/EBPδ at different steps of the metastatic cascade, using established in vitro models. We found that C/EBPδ has a major impact on cell motility, an important prerequisite for tumor cells to leave the primary tumor and to reach distant sites. Our data suggest that C/EBPδ induces downstream pathways that modulate actin cytoskeleton dynamics to reduce cell migration and to induce a more epithelial-like cellular phenotype. Understanding the mechanisms dictating epithelial and mesenchymal features holds great promise for improving the treatment of PDAC.https://www.mdpi.com/2073-4409/11/21/3334CCAAT/enhancer-binding protein deltapancreatic ductal adenocarcinomametastasesmigrationcytoskeleton |
| spellingShingle | Leonie Hartl Pien A. F. Maarschalkerweerd Joe M. Butler Xue D. Manz Victor L. J. L. Thijssen Maarten F. Bijlsma JanWillem Duitman C. Arnold Spek C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell Migration Cells CCAAT/enhancer-binding protein delta pancreatic ductal adenocarcinoma metastases migration cytoskeleton |
| title | C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell Migration |
| title_full | C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell Migration |
| title_fullStr | C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell Migration |
| title_full_unstemmed | C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell Migration |
| title_short | C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell Migration |
| title_sort | c ebpδ suppresses motility associated gene signatures and reduces pdac cell migration |
| topic | CCAAT/enhancer-binding protein delta pancreatic ductal adenocarcinoma metastases migration cytoskeleton |
| url | https://www.mdpi.com/2073-4409/11/21/3334 |
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