C/EBPδ Suppresses Motility-Associated Gene Signatures and Reduces PDAC Cell Migration

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cells, Vol 11, Iss 21, p 3334 (2022)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells11213334
Popis: 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.
Databáze: Directory of Open Access Journals
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