title: Downregulation of cylindromatosis gene, CYLD, confers a growth advantage             on malignant melanoma cells while negatively regulating their migration activity.
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.
authors.affiliation: Department of Tumor Biology, Institute of Biomedical Science,                     Iwate Medical University, Iwate, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Kanako
authors.initials: K
authors.lastname: Tsunoda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibazaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Akasaka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.forename: Chihaya
authors.initials: C
authors.lastname: Maesawa
mesh_terms: D000107:Acetylation; D000081242:B-Cell Lymphoma 3 Protein; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000074749:Deubiquitinating Enzyme CYLD; D015536:Down-Regulation; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D034921:Lamin Type B / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008870:Microtubules / Q000378:metabolism; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D034921:Lamin Type B; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D014404:Tubulin; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D020830:rac1 GTP-Binding Protein