Human NRAGE disrupts E-cadherin/beta-catenin regulated homotypic cell-cell adhesion.
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.
Xue
Bin
B
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing 210097, PR China.
Wen
Chuanjun
C
Shi
Yihuan
Y
Zhao
Donghong
D
Li
Chaojun
C
D000818:Animals; D000951:Antigens, Neoplasm; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D051176:beta Catenin
D000951:Antigens, Neoplasm; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; C120897:MAGED1 protein, human; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin