title: MRP-1/CD9 gene transduction downregulates Wnt signal pathways.
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.
authors.affiliation: The Second Department of Surgery, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, 761-0793, Japan. chuang@kms.ac.jp
authors.forename: Cheng-long
authors.initials: CL
authors.lastname: Huang
authors.forename: Dage
authors.initials: D
authors.lastname: Liu
authors.forename: Daiki
authors.initials: D
authors.lastname: Masuya
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kameyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakashima
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yokomise
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyake
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics*; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D060245:Tetraspanin 29; D014161:Transduction, Genetic
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29