Abstract
Pancreatic cancer is the fourth most common lethal malignancy with an overall 5-year survival rate of less than 5%. ERas, a novel Ras family member, was first identified in murine embryonic stem cells and is upregulated in various cancers. However, the expression and potential role of ERas in pancreatic cancer have not been investigated. In this study, we found that ERas mRNA and protein were upregulated in pancreatic cancer tissues and cells compared with controls. Knockdown of ERas in pancreatic cancer cells by siRNA significantly decreased cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis in vitro. Epithelial–mesenchymal transition (EMT) is closely related to tumor progression. We observed a significant decrease in N-cadherin expression in pancreatic cancer cells in response to ERas gene silencing by immunofluorescence assay and western blot. Furthermore, tumor growth and EMT were inhibited in xenografts derived from pancreatic cancer cells with ERas downregulation. We further investigated the regulatory mechanisms of ERas in pancreatic cancer and found that ERas may activate the Erk/Akt signaling pathway. Moreover, Erk inhibitor decreased pancreatic cancer cells proliferation and colony formation activities. Our data suggest that targeting ERas and its relevant signaling pathways might represent a novel therapeutic approach for the treatment of pancreatic cancer.
Highlights
Pancreatic cancer is the fourth leading cause of cancerrelated mortalities with rapid progression and dismal prognosis [1,2,3,4,5]
To determine whether ERas is involved in the development of pancreatic cancer, we first analyzed ERas mRNA and protein expression in human pancreatic duct epithelial (HPDE) and pancreatic cancer cell lines by real-time PCR and western blot analysis
Both ERas mRNA and protein expression were detected in all five pancreatic cancer cell lines, while no expression was detected in the HPDE cell line (Fig. 1a, b)
Summary
Pancreatic cancer is the fourth leading cause of cancerrelated mortalities with rapid progression and dismal prognosis [1,2,3,4,5]. The median survival rate of pancreatic cancer is less than 6 months [6,7,8]. Chemotherapy plays an important role in the treatment of pancreatic cancer. Pancreatic cancer can show intrinsic resistance to chemotherapy, resulting in aggressive local invasion and early metastasis. Embryonic stem (ES) cells are pluripotent cells that maintain differentiation ability [12]. Due to their rapid growth and immortality, ES cells have been used in stem cell therapies. ES cells and tumor cells most likely share common growth properties
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