Abstract
BackgroundPancreatic cancer has a high mortality rate because it is usually diagnosed when metastasis have already occurred (microscopic and gross disease). Ezrin plays important roles in cell motility, invasion and tumor progression, and it is especially crucial for metastasis. However, its function in pancreatic cancer remains elusive.Methods and ResultsWe found that ezrin overexpression promoted cell protrusion, microvillus formation, anchorage-independent growth, motility and invasion in a pancreatic cancer cell line, MiaPaCa-2, whereas ezrin silencing resulted in the opposite effects. Ezrin overexpression also increased the number of metastatic foci (6/8 vs. 1/8) in a spontaneous metastasis nude mouse model. Furthermore, ezrin overexpression activated Erk1/2 in MiaPaCa-2 cells, which might be partially related to the alteration of cell morphology and invasion. Immunohistochemical analysis showed that ezrin was overexpressed in pancreatic ductal adenocarcinoma (PDAC) (91.4%) and precancerous lesions, i.e. the tubular complexes in chronic pancreatitis (CP) and pancreatic intraepithelial neoplasm (PanIN) (85.7% and 97.1%, respectively), compared to normal pancreatic tissues (0%). Ezrin was also expressed in intercalated ducts adjacent to the adenocarcinoma, which has been considered to be the origin of ducts and acini, as well as the starting point of pancreatic ductal carcinoma development.ConclusionsWe propose that ezrin might play functional roles in modulating morphology, growth, motility and invasion of pancreatic cancer cells, and that the Erk1/2 pathway may be involved in these roles. Moreover, ezrin may participate in the early events of PDAC development and may promote its progression to the advanced stage.
Highlights
Pancreatic cancer has a high mortality rate because it is usually diagnosed when metastasis have already occurred
We propose that ezrin might play functional roles in modulating morphology, growth, motility and invasion of pancreatic cancer cells, and that the Erk1/2 pathway may be involved in these roles
We investigated the effect of ezrin on the motility and invasion ability of the pancreatic cancer cell line MiaPaCa-2, as well as the expression of ezrin in pancreatic duct adenocarcinoma, chronic pancreatitis and normal pancreatic tissues
Summary
Pancreatic cancer has a high mortality rate because it is usually diagnosed when metastasis have already occurred (microscopic and gross disease). Ezrin plays important roles in cell motility, invasion and tumor progression, and it is especially crucial for metastasis. Ezrin plays important roles in cell motility, morphogenesis, adhesion, survival and apoptosis [1,2,3,4,5,6]. It participates in crucial signal transduction pathways [7]. Ezrin binds to cell surface glycoproteins, such as CD43, CD44, ICAM-1 and ICAM-2, through interacting with their amino (N)-terminal domains. Ezrin has been linked to molecules that control the phosphatidylinositol-3-kinase, AKT, Erk1/2 MAPK and Rho pathways, which are functionally involved in signaling events regulating cell survival, proliferation and migration.
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