NRAGE suppresses metastasis of melanoma and pancreatic cancer in vitro and in vivo.
We previously reported that human NRAGE could significantly alter the cellular skeleton and inhibit cell-cell adhesion, suggesting that human NRGAE play a potential role in cellular motility. Here, we report overexpression of human NRAGE in PANC-1 and B16-Bl6 cells could significantly suppress the metastasis of these cells in vitro and in vivo. Consistently, PANC-1 with stable silencing of NRAGE by RNA interference, exhibits a more metastatic phenotype than the native cell. Expression of epithelial proteins, including E-cadherin and beta-catenin is down regulated in siRNA-NRAGE PANC-1 cells. Further studies find that overexpression of human NRAGE suppresses the mRNA expression and activity of MMP2 significantly. Summary, our studies indicate for the first time that NRAGE could suppress metastasis of melanoma and pancreatic cancer probably through downregulation of MMP-2.
Chu
Chao-shun
CS
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing 210097, PR China.
Xue
Bin
B
Tu
Chen
C
Feng
Zhen-hua
ZH
Shi
Yi-huan
YH
Miao
Yi
Y
Wen
Chuan-Jun
CJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D017931:DNA Primers; D020868:Gene Silencing; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D017931:DNA Primers; C120897:MAGED1 protein, human; D009363:Neoplasm Proteins