title: Ezrin promotes invasion and metastasis of pancreatic cancer cells.
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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Meng
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Lu
authors.forename: Shuangni
authors.initials: S
authors.lastname: Yu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yihui
authors.initials: Y
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology / Q000473:pathology; D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D022081:Cell Surface Extensions / Q000648:ultrastructure; D002999:Clone Cells; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008871:Microvilli / Q000648:ultrastructure; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000473:pathology; D010766:Phosphorylation; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D000099149:Ezrin