Downregulation of cylindromatosis gene, CYLD, confers a growth advantage on malignant melanoma cells while negatively regulating their migration activity

  • Authors:
    • Yuichi Ishikawa
    • Kanako Tsunoda
    • Masahiko Shibazaki
    • Kazuhiro Takahashi
    • Toshihide Akasaka
    • Tomoyuki Masuda
    • Chihaya Maesawa
  • View Affiliations

  • Published online on: April 2, 2012     https://doi.org/10.3892/ijo.2012.1424
  • Pages: 53-60
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Abstract

The cylindromatosis gene (CYLD) encodes a deubiquitinase that was initially identified as a tumor suppressor and has recently been investigated in connection with a variety of normal physiological processes. In contrast to its cell-proliferative activity, the effect of CYLD protein on cell migration has been a matter of debate. We investigated the effect of CYLD-siRNA on the migration activity of malignant melanoma cells. Expression of CYLD mRNA/protein was lower in 6 of 8 malignant melanoma cell lines than in 3 sets of primary-cultured normal human epidermal melanocytes. Knockdown of CYLD significantly increased the proliferation activities of two melanoma cell lines (p<0.05), along with BCL3 nuclear translocation followed by CCND1 overexpression. In contrast to the proliferation-related activity, CYLD knockdown significantly decreased the cell migration of all the melanoma cell lines (n=7, p<0.05), and we demonstrated that the mechanism regulating melanoma cell migration was activation of RAC1 through the action of CYLD. Our findings provide new insight into the role of CYLD-induced RAC1 activation in melanoma cell migration.

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July 2012
Volume 41 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ishikawa Y, Tsunoda K, Shibazaki M, Takahashi K, Akasaka T, Masuda T and Maesawa C: Downregulation of cylindromatosis gene, CYLD, confers a growth advantage on malignant melanoma cells while negatively regulating their migration activity. Int J Oncol 41: 53-60, 2012
APA
Ishikawa, Y., Tsunoda, K., Shibazaki, M., Takahashi, K., Akasaka, T., Masuda, T., & Maesawa, C. (2012). Downregulation of cylindromatosis gene, CYLD, confers a growth advantage on malignant melanoma cells while negatively regulating their migration activity. International Journal of Oncology, 41, 53-60. https://doi.org/10.3892/ijo.2012.1424
MLA
Ishikawa, Y., Tsunoda, K., Shibazaki, M., Takahashi, K., Akasaka, T., Masuda, T., Maesawa, C."Downregulation of cylindromatosis gene, CYLD, confers a growth advantage on malignant melanoma cells while negatively regulating their migration activity". International Journal of Oncology 41.1 (2012): 53-60.
Chicago
Ishikawa, Y., Tsunoda, K., Shibazaki, M., Takahashi, K., Akasaka, T., Masuda, T., Maesawa, C."Downregulation of cylindromatosis gene, CYLD, confers a growth advantage on malignant melanoma cells while negatively regulating their migration activity". International Journal of Oncology 41, no. 1 (2012): 53-60. https://doi.org/10.3892/ijo.2012.1424