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CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells

  1. Tomomi Sakuma1,2,3,
  2. Tetsuya Nakamoto1,2,*,
  3. Hiroaki Hemmi1,4,
  4. Sohei Kitazawa5,
  5. Riko Kitazawa6,
  6. Takuya Notomi1,2,
  7. Tadayoshi Hayata1,
  8. Yoichi Ezura1,
  9. Teruo Amagasa3,
  10. Masaki Noda1,2,*

Article first published online: 20 MAR 2012

DOI: 10.1002/jcp.24066

Issue

Journal of Cellular Physiology

Journal of Cellular Physiology

Volume 227, Issue 7, pages 2807–2812, July 2012

Additional Information

How to Cite

Sakuma, T., Nakamoto, T., Hemmi, H., Kitazawa, S., Kitazawa, R., Notomi, T., Hayata, T., Ezura, Y., Amagasa, T. and Noda, M. (2012), CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells. J. Cell. Physiol., 227: 2807–2812. doi: 10.1002/jcp.24066

Author Information

  1. 1

    Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

  2. 2

    Global-COE Program, Tokyo Medical and Dental University, Tokyo, Japan

  3. 3

    Maxillofacial Surgery, Tokyo Medical and Dental University, Tokyo, Japan

  4. 4

    Medical Top Track Program, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

  5. 5

    Ehime University Graduate School of Medicine Division of Molecular Pathology, Ehime, Japan

  6. 6

    Kobe University Division of Molecular Pathology, Kobe, 650-0017, Japan

*Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yusima Bunkyo-ku, Tokyo 113-8510, Japan.

Publication History

  1. Issue published online: 20 MAR 2012
  2. Article first published online: 20 MAR 2012
  3. Accepted manuscript online: 3 FEB 2012 01:53PM EST
  4. Manuscript Accepted: 24 JAN 2012
  5. Manuscript Received: 21 JAN 2012

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Abstract

Tumor metastasis to bone is a serious pathological situation that causes severe pain, and deterioration in locomoter function. However, the mechanisms underlying tumor metastasis is still incompletely understood. CIZ/NMP4 is a nucleocytoplasmic shuttling protein and its roles in tumor cells have not been known. We, therefore, hypothesized the role of CIZ/NMP4 in B16 melanoma cells that metastasize to bone. CIZ/NMP4 is expressed in B16 cells. The CIZ/NMP4 expression levels are correlated to the metastatic activity in divergent types of melanoma cells. Overexpression of CIZ/NMP4 increased B16 cell migration in Trans-well assay. Conversely, siRNA-based knockdown of CIZ/NMP4 suppressed migratory activity of these cells. As RANKL promotes metastasis of tumor cells in bone, we tested its effect on CIZ in melanoma cells. RANKL treatment enhanced CIZ/NMP4 expression. This increase of CIZ by RANKL promoted migration. Conversely, we identified CIZ/NMP4 binding site in the promoter of RANKL. Furthermore, luciferase assay indicated that CIZ/NMP4 overexpression enhanced RANKL promoter activities, revealing a positive feedback loop of CIZ/NMP4 and RANKL in melanoma. These observations indicate that CIZ/NMP4 is critical regulator of metastasis of melanoma cells. J. Cell. Physiol. 227: 2807–2812, 2012. © 2012 Wiley Periodicals, Inc.

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