Loss of Pim1 Imposes a Hyperadhesive Phenotype on Endothelial Cells
| Autor: | Elvira Haas, Edouard Battegay, Jürg Schwaller, Rok Humar, Thomas Walpen, Martin Peier, Ina Kalus |
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| Přispěvatelé: | University of Zurich, Humar, Rok |
| Rok vydání: | 2012 |
| Předmět: |
Physiology
610 Medicine & health Biology Transfection Extracellular matrix Adherens junction Focal adhesion 03 medical and health sciences Mice 0302 clinical medicine Proto-Oncogene Proteins c-pim-1 Cell Movement Cell Adhesion Animals Humans Cell adhesion Aorta Cells Cultured 030304 developmental biology Mice Knockout 0303 health sciences Focal Adhesions Wound Healing Cadherin Endothelial Cells Cell migration 1314 Physiology Adherens Junctions Molecular biology Cell biology Trypsinization 030220 oncology & carcinogenesis 10076 Center for Integrative Human Physiology 570 Life sciences biology 10029 Clinic and Policlinic for Internal Medicine Wound healing Gene Deletion |
| Zdroj: | Cellular physiology and biochemistry : international journal of experimental cellular physiology bi CELLULAR PHYSIOLOGY AND BIOCHEMISTRY |
| DOI: | 10.1159/000341484 |
| Popis: | 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. Conclusion: 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. |
| Databáze: | OpenAIRE |
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