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MRP-1/CD9 gene transduction downregulates Wnt signal pathways

Oncogene volume 23, pages 7475–7483 (2004)Cite this article

Abstract

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.

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Authors and Affiliations

  1. The Second Department of Surgery, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Cheng-long Huang, Dage Liu, Daiki Masuya, Kotaro Kameyama, Takashi Nakashima & Hiroyasu Yokomise

  2. Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan

    Masaki Ueno

  3. The Fifth Department of Oncology and the Department of Thoracic Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, 530-8480, Japan

    Masayuki Miyake

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  1. Cheng-long Huang
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Correspondence to Cheng-long Huang.

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Huang, Cl., Liu, D., Masuya, D. et al. MRP-1/CD9 gene transduction downregulates Wnt signal pathways. Oncogene 23, 7475–7483 (2004). https://doi.org/10.1038/sj.onc.1208063

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