Human NRAGE Disrupts E-cadherin/beta-catenin Regulated Homotypic Cell-Cell Adhesion

Biochem Biophys Res Commun. 2005 Oct 14;336(1):247-51. doi: 10.1016/j.bbrc.2005.08.069.

Abstract

Human NRAGE, a neurotrophin receptor p75 interaction MAGE homologue, confers NGF-dependent apoptosis of neuronal cells by inducing caspase activation through the JNK-c-jun-dependent pathway and arrests cell growth through the p53-dependent pathway. Our findings showed that human NRAGE could significantly alter the cell skeleton and inhibit homotypic cell-cell adhesion in U2OS cells. With further experiments, we revealed that human NRAGE disrupts colocalization of the E-cadherin/beta-catenin complex and translocates beta-catenin from the cell membrane into the cytoplasm and nucleus. Synchronously, NRAGE also decreases the total protein level of beta-catenin, especially when NRAGE expresses for a long time. More importantly, knock down of NRAGE by RNA interference in PANC-1 cell significantly reinforces E-cadherin/beta-catenin homotypic cell adhesion. The data demonstrate the importance of human NRAGE in homotypic cell-to-cell adhesion and illuminate the mechanism of human NRAGE in the process of inhibition of cell adhesion, which suggests that human NRGAE plays a potential negative role in cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm
  • Cadherins / physiology*
  • Cell Adhesion / physiology*
  • Cell Line
  • Cytoskeletal Proteins / physiology*
  • Humans
  • Neoplasm Proteins / physiology*
  • Subcellular Fractions / metabolism
  • Trans-Activators / physiology*
  • beta Catenin

Substances

  • Antigens, Neoplasm
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • MAGED1 protein, human
  • Neoplasm Proteins
  • Trans-Activators
  • beta Catenin