Scientific article

Raf kinase inhibitor protein positively regulates cell-substratum adhesion while negatively regulating cell-cell adhesion

Published inJournal of cellular biochemistry, vol. 103, no. 3, p. 972-985
Publication date2008

Raf kinase inhibitor protein (RKIP) regulates a number of cellular processes, including cell migration. Exploring the role of RKIP in cell adhesion, we found that overexpression of RKIP in Madin-Darby canine kidney (MDCK) epithelial cells increases adhesion to the substratum, while decreasing adhesion of the cells to one another. The level of the adherens junction protein E-cadherin declines profoundly, and there is loss of normal localization of the tight junction protein ZO-1, while expression of the cell-substratum adhesion protein beta1 integrin dramatically increases. The cells also display increased adhesion and spreading on multiple substrata, including collagen, gelatin, fibronectin and laminin. In three-dimensional culture, RKIP overexpression leads to marked cell elongation and extension of long membrane protrusions into the surrounding matrix, and the cells do not form hollow cysts. RKIP-overexpressing cells generate considerably more contractile traction force than do control cells. In contrast, RNA interference-based silencing of RKIP expression results in decreased cell-substratum adhesion in both MDCK and MCF7 human breast adenocarcinoma cells. Treatment of MDCK and MCF7 cells with locostatin, a direct inhibitor of RKIP and cell migration, also reduces cell-substratum adhesion. Silencing of RKIP expression in MCF7 cells leads to a reduction in the rate of wound closure in a scratch-wound assay, although not as pronounced as that previously reported for RKIP-knockdown MDCK cells. These results suggest that RKIP has important roles in the regulation of cell adhesion, positively controlling cell-substratum adhesion while negatively controlling cell-cell adhesion, and underscore the complex functions of RKIP in cell physiology.

  • Adherens Junctions/metabolism
  • Animals
  • Antigens, CD29/metabolism
  • Breast Neoplasms/metabolism/pathology
  • Cadherins/metabolism
  • Cell Movement/drug effects
  • Cell-Matrix Junctions/drug effects/metabolism
  • Dogs
  • Down-Regulation
  • Epithelial Cells/metabolism
  • Extracellular Matrix/metabolism
  • Extracellular Matrix Proteins/chemistry/metabolism
  • Humans
  • Kidney Neoplasms/metabolism/pathology
  • Membrane Proteins/metabolism
  • Oxazolidinones/pharmacology
  • Phosphatidylethanolamine Binding Protein/metabolism/pharmacology
  • Phosphoproteins/metabolism
  • Protein Kinase Inhibitors/metabolism/pharmacology
  • RNA Interference
  • Tumor Cells, Cultured
  • Up-Regulation
  • Wound Healing/drug effects
  • Raf Kinases/antagonists & inhibitors
Citation (ISO format)
MC HENRY, Kevin T. et al. Raf kinase inhibitor protein positively regulates cell-substratum adhesion while negatively regulating cell-cell adhesion. In: Journal of cellular biochemistry, 2008, vol. 103, n° 3, p. 972–985. doi: 10.1002/jcb.21470
Main files (1)
Article (Accepted version)
ISSN of the journal1097-4644

Technical informations

Creation06/19/2009 11:55:00 AM
First validation06/19/2009 11:55:00 AM
Update time03/14/2023 3:09:08 PM
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