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MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2

Oncogene volume 25, pages 6480–6488 (2006)Cite this article

Abstract

Motility-related protein-1 (MRP-1/CD9) is involved in cell motility. We studied the change in the actin cytoskeleton, and the expression of actin-related protein (Arp) 2 and Arp3 and the Wiskott–Aldrich syndrome protein (WASP) family according to MRP-1/CD9 gene transduction into HT1080 cells. The frequency of cells with lamellipodia was significantly lower in MRP-1/CD9-transfected HT1080 cells than in control HT1080 cells (P<0.0001). MRP-1/CD9 gene transduction affected the subcellular localization of Arp2 and Arp3 proteins. Furthermore, MRP-1/CD9 gene transduction induced a downregulation of WAVE2 expression (P<0.0001). However, no difference was observed in the expression of Arp2, Arp3 or other WASPs. A neutralizing anti-MRP-1/CD9 monoclonal antibody inhibited downregulation of WAVE2 in MRP-1/CD9-transfected HT1080 cells (P<0.0001), and reversed the morphological effects of MRP-1/CD9 gene transduction. Furthermore, downregulation of WAVE2 by transfection of WAVE2-specific small interfering RNA (siRNA) mimicked the morphological effects of MRP-1/CD9 gene transduction and suppressed cell motility. However, transfection of each siRNA for Wnt1, Wnt2b1 or Wnt5a did not affect WAVE2 expression. Transfection of WAVE2-specific siRNA also did not affect expressions of these Wnts. These results indicate that MRP-1/CD9 regulates the actin cytoskeleton by downregulating of the WAVE2, through the Wnt-independent signal pathway.

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Authors and Affiliations

  1. The Second Department of Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan

    C-L Huang, D Liu, D Masuya, J Nakano & H Yokomise

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

    M Ueno

  3. Life Science Research Center, Kagawa University, Kagawa, Japan

    T Nakagawa

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

    M Miyake

Authors
  1. C-L Huang
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  2. M Ueno
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  3. D Liu
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  4. D Masuya
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  5. J Nakano
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  6. H Yokomise
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  7. T Nakagawa
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Correspondence to C-L Huang.

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Huang, CL., Ueno, M., Liu, D. et al. MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2. Oncogene 25, 6480–6488 (2006). https://doi.org/10.1038/sj.onc.1209654

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