Silencing Delta-like 1 Expression Induces Migratory Features in Pancreatic Cancer Cells Through Stimulation of Src and p38 Signalling Pathway.

Abstract

The prognosis of pancreatic cancer has not improved due to its migratory feature and refractory potential to chemo-resistance with absence of effective diagnosis. Despite continuous efforts, its underlying mechanisms of malignant nature remain ambiguous. The objective of this study was to investigate delta-like 1 (DLL1) as a tumor suppressor in the metastasic ability of human pancreatic cancer cells. Cellular expression of DLL1 was demonstrated using the GEO public database and western blot analysis. The biological function of DLL1 was validated by biological behavior analysis. Prognosis to DLL1 expression was demonstrated using analysis of the GEO public database. Analysis using the GEO database and western blotting showed higher DLL1 mRNA and protein expression levels in pancreatic cancer compared to those in normal pancreas. DLL1 was uniquely expressed in seven human pancreatic cancer cell lines compared to human pancreatic duct epithelial H6c7 cells. Ablation of DLL1 expression stimulated migration and invasion by activating Src and p38 phosphorylation, but not viability and chemo-resistance of human pancreatic cancer cells. In addition, expression of DLL1 was correlated with migratory features of pancreatic cancer in vivo. Moreover, high DLL1 expression was associated with a favorable prognosis in pancreatic cancer patients. DLL1 is a potent suppressor of pancreatic cancer metastasis. Understanding correlation between expression and function of DLL1 might contribute to our knowledge of the complicated mechanism of pancreatic cancer metastasis.