MRP-1/ CD9 gene transduction downregulates Wnt signal pathways.
Motility-related protein-1 ( MRP-1/ CD9) is a transmembrane glycoprotein that has been implicated in cell adhesion, motility, proliferation, and differentiation. It has a functional role as a tumor metastatic suppressor. During tumor progression, a reduction of MRP-1/ CD9 gene expression results in tumor cells with a high metastatic potential. However, the mechanism of action of MRP-1/ CD9 is still unclear. We studied changes of gene expression in relation to MRP-1/ CD9 gene transduction into tumor cell lines, HT1080 and A549, using microarray assays and real-time PCR. Consequently, we have demonstrated that MRP-1/ CD9 gene transduction can downregulate expression of several Wnt family genes, such as Wnt1, Wnt2b1 and Wnt5a, and their target genes, including WISP-1 (Wnt-1 induced secreted protein 1), WISP-3, c-Myc, vascular endothelial growth factor-A, and matrix metalloproteinase-26. Western blot analyses also showed that MRP-1/ CD9 gene transduction downregulated expression of Wnt1 protein and its target proteins. In addition, a neutralizing anti-MRP-1/ CD9 monoclonal antibody inhibited the downregulation of Wnt signal pathways in MRP-1/CD9-transfected cells. The present study has revealed that the MRP-1/ CD9 signal is located upstream of the Wnt signal pathways. Therefore, MRP-1/ CD9 could suppress cell transformation including epithelial to mesenchymal transition through downregulation of Wnt1, and might suppress tumor metastasis through downregulation of Wnt5a.[1]References
- MRP-1/CD9 gene transduction downregulates Wnt signal pathways. Huang, C.L., Liu, D., Masuya, D., Kameyama, K., Nakashima, T., Yokomise, H., Ueno, M., Miyake, M. Oncogene (2004) [Pubmed]
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