CCAAT/enhancer-binding protein δ (C/EBPδ) is a
transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor
tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in
glioblastoma and promotes
genomic instability in
cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in
pancreatic cancer. We determined C/EBPδ expression in biopsies from
pancreatic cancer patients using public gene-expression datasets and in-house tissue microarrays. We found that C/EBPδ is highly expressed in healthy pancreatic ductal cells but lost in pancreatic ductal
adenocarcinoma. Furthermore, loss of C/EBPδ correlated with increased lymph node involvement and shorter overall survival in pancreatic ductal
adenocarcinoma patients. In accordance with this, in vitro experiments showed reduced clonogenic capacity and proliferation of pancreatic ductal
adenocarcinoma cells following C/EBPδ re-expression, concurrent with decreased sphere formation capacity in soft
agar assays. We thus report a previously unrecognized but important
tumor suppressor role of C/EBPδ in pancreatic ductal
adenocarcinoma. This is of particular interest since only few
tumor suppressors have been identified in the context of
pancreatic cancer. Moreover, our findings suggest that restoration of C/EBPδ activity could hold therapeutic value in pancreatic ductal
adenocarcinoma, although the latter claim needs to be substantiated in future studies.