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

Ishikawa,Yuichi; Tsunoda,Kanako; Shibazaki,Masahiko; Takahashi,Kazuhiro; Akasaka,Toshihide; Masuda,Tomoyuki; Maesawa,Chihaya

doi:10.3892/ijo.2012.1424

July 2012 Volume 41 Issue 1

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July 2012 Volume 41 Issue 1

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Article

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 / Copyright

Affiliations: Department of Tumor Biology, Institute of Biomedical Science, Iwate Medical University, Iwate, Japan, Department of Dermatology, School of Medicine, Iwate Medical University, Iwate, Japan, Department of Pathology, School of Medicine, Iwate Medical University, Iwate, Japan
Pages: 53-60
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Published online on: April 2, 2012

https://doi.org/10.3892/ijo.2012.1424
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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.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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Abstract

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