Xue B, Wen C, Shi Y, Zhao D, Li C

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 ...

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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.

Date: Oct. 14, 2005

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