title: Loss of pim1 imposes a hyperadhesive phenotype on endothelial cells.
abstract: BACKGROUND
  PIM1 is a constitutively active serine-threonine kinase regulating cell survival and proliferation. Increased PIM1 expression has been correlated with cancer metastasis by facilitating migration and anti-adhesion. Endothelial cells play a pivotal role in these processes by contributing a barrier to the blood stream. Here, we investigated whether PIM1 regulates mouse aortic endothelial cell (MAEC) monolayer integrity.
  
  
  METHODS
  Pim1-/-MAEC were isolated from Pim1 knockout mice and used in trypsinization-, wound closure assays, electrical cell-substrate sensing, immunostaining, cDNA transfection and as RNA source for microarray analysis.
  
  
  RESULTS
  Pim1-/-MAEC displayed decreased migration, slowed cell detachment and increased electrical resistance across the endothelial monolayer. Reintroduction of Pim1- cDNA into Pim1-/-MAEC significantly restored wildtype adhesive characteristics. Pim1-/--MAEC displayed enhanced focal adhesion and adherens junction structures containing vinculin and β-catenin, respectively. Junctional molecules such as Cadherin 13 and matrix components such as Collagen 6a3 were highly upregulated in Pim1-/- cells. Intriguingly, extracellular matrix deposited by Pim1-/- cells alone was sufficient to induce the hyperadhesive phenotype in wildtype endothelial cells.
  
  
  CONCLUSIONS
  Loss of Pim1 induces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix. Targeting PIM1 function therefore might be important to promote endothelial barrier integrity.
authors.affiliation: Research Unit, Division Internal Medicine, University Hospital Zürich, Zürich, Schweiz.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walpen
authors.forename: Martin
authors.initials: M
authors.lastname: Peier
authors.forename: Elvira
authors.initials: E
authors.lastname: Haas
authors.forename: Ina
authors.initials: I
authors.lastname: Kalus
authors.forename: Jürg
authors.initials: J
authors.lastname: Schwaller
authors.forename: Edouard
authors.initials: E
authors.lastname: Battegay
authors.forename: Rok
authors.initials: R
authors.lastname: Humar
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014945:Wound Healing
chemical_list: C496634:PIM1 protein, human; C496636:Pim1 protein, mouse; D051573:Proto-Oncogene Proteins c-pim-1