title: Peroxiredoxin 1 promotes pancreatic cancer cell invasion by modulating p38 MAPK activity.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of peroxiredoxin 1 (Prdx1) in the invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells.
  
  
  METHODS
  Immunohistochemistry was used to determine overexpression of Prdx1 in human PDAC tissues. Immunoprecipitation and immunocytochemistry were used to determine the interaction and intracellular distribution of Prdx1 and a member of the mitogen-activated protein kinase (MAPK) family protein, p38 MAPK, in PDAC cells. Finally, immunocytochemistry and Matrigel invasion assay were used to examine the effects of Prdx1 and p38 MAPK on the formation of cell protrusions and PDAC cell invasion.
  
  
  RESULTS
  Prdx1 is overexpressed in human PDAC tissues. Peroxiredoxin 1 interacts with active forms of p38 MAPK, and complexes of Prdx1 and phosphorylated p38 MAPK localize at the leading edges of migrating PDAC cells. Suppression of Prdx1 decreases active p38 MAPK localized in cell protrusions and inhibits the invasiveness of PDAC cells. Consequently, suppression of Prdx1 inhibits membrane ruffling and protrusions. The p38 MAPK inhibitor SB203580 also decreases the formation of membrane protrusions and inhibits invasiveness.
  
  
  CONCLUSIONS
  Prdx1 associates with the formation of membrane protrusions through modulation of the activity of p38 MAPK, which in turn promotes PDAC cell invasion.
authors.affiliation: From the Departments of *Pharmacology, †Pathology, ‡Surgery, and §Gastroenterology and Hepatology, School of Medicine, Kochi University, Nankoku, Kochi, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taniuchi
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hanazaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Iwasaki
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D048051:p38 Mitogen-Activated Protein Kinases