Ezrin promotes invasion and metastasis of pancreatic cancer cells
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RESEARCH
Open Access
Ezrin promotes invasion and metastasis of pancreatic cancer cells Yunxiao Meng, Zhaohui Lu, Shuangni Yu, Qiang Zhang, Yihui Ma, Jie Chen*
Abstract Background: 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. However, its function in pancreatic cancer remains elusive. Methods and Results: We 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. Conclusions: 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. Moreover, ezrin may participate in the early events of PDAC development and may promote its progression to the advanced stage.
Background Ezrin, encoded by the Vil2 gene, is a member of the ERM family; it provides a functional link between the plasma membrane and the cortical actin cytoskeleton of the cell. Ezrin plays important roles in cell motility, morphogenesis, adhesion, survival and apoptosis [1-6]. It also 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 also binds to filamentous actin through its carboxyl (C)-terminal domains [8]. 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. Phosphorylation of ezrin * Correspondence: [email protected] Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing, China
induces its translocation from the cytoplasm to the plasma membranes of microvillus and c
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