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

作者：Ishikawa Yuichi; Tsunoda Kanako; Shibazaki Masahiko; Takahashi Kazuhiro; Akasaka Toshihide; Masuda Tomoyuki; Maesawa Chihaya^*

来源：International Journal of Oncology, 2012, 41(1): 53-60.

DOI：10.3892/ijo.2012.1424

• melanoma
• CYLD
• migration
• proliferation
• HDAC6

The cylindromatosis gene (CYLD) encodes a deubiq-uitinase 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.

• 出版日期2012-7