CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells
| Autor: | Masaki Noda, Tetsuya Nakamoto, Tadayoshi Hayata, Teruo Amagasa, Riko Kitazawa, Takuya Notomi, Yoichi Ezura, Tomomi Sakuma, Sohei Kitazawa, Hiroaki Hemmi |
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| Rok vydání: | 2012 |
| Předmět: |
Physiology
Clinical Biochemistry Cell Regulator Melanoma Experimental Bone Neoplasms Metastasis Mice Nuclear Matrix-Associated Proteins Cell Movement medicine Cell Adhesion Tumor Cells Cultured Animals Luciferase Neoplasm Metastasis Promoter Regions Genetic Feedback Physiological Gene knockdown Binding Sites biology Melanoma RANK Ligand Cell migration Cell Biology medicine.disease Up-Regulation Mice Inbred C57BL medicine.anatomical_structure RANKL biology.protein Cancer research Transcription Factors |
| Zdroj: | Journal of cellular physiology. 227(7) |
| ISSN: | 1097-4652 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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