Human NRAGE disrupts E-cadherin/beta-catenin regulated homotypic cell-cell adhesion.

Bin Xue, Chuanjun Wen, Yihuan Shi, Donghong Zhao, Chaojun Li

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing 210097, PR China.

Biochemical and biophysical research communications 2005 Oct 14

filter terms:

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.

Citation

Bin Xue, Chuanjun Wen, Yihuan Shi, Donghong Zhao, Chaojun Li. Human NRAGE disrupts E-cadherin/beta-catenin regulated homotypic cell-cell adhesion. Biochemical and biophysical research communications. 2005 Oct 14;336(1):247-51