title: Truncated SSX protein suppresses synovial sarcoma cell proliferation by inhibiting the localization of SS18-SSX fusion protein.
abstract: Synovial sarcoma is a relatively rare high-grade soft tissue sarcoma that often develops in the limbs of young people and induces the lung and the lymph node metastasis resulting in poor prognosis. In patients with synovial sarcoma, specific chromosomal translocation of t(X; 18) (p11.2;q11.2) is observed, and SS18-SSX fusion protein expressed by this translocation is reported to be associated with pathogenesis. However, role of the fusion protein in the pathogenesis of synovial sarcoma has not yet been completely clarified. In this study, we focused on the localization patterns of SS18-SSX fusion protein. We constructed expression plasmids coding for the full length SS18-SSX, the truncated SS18 moiety (tSS18) and the truncated SSX moiety (tSSX) of SS18-SSX, tagged with fluorescent proteins. These plasmids were transfected in synovial sarcoma SYO-1 cells and we observed the expression of these proteins using a fluorescence microscope. The SS18-SSX fusion protein showed a characteristic speckle pattern in the nucleus. However, when SS18-SSX was co-expressed with tSSX, localization of SS18-SSX changed from speckle patterns to the diffused pattern similar to the localization pattern of tSSX and SSX. Furthermore, cell proliferation and colony formation of synovial sarcoma SYO-1 and YaFuSS cells were suppressed by exogenous tSSX expression. Our results suggest that the characteristic speckle localization pattern of SS18-SSX is strongly involved in the tumorigenesis through the SSX moiety of the SS18-SSX fusion protein. These findings could be applied to further understand the pathogenic mechanisms, and towards the development of molecular targeting approach for synovial sarcoma.
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan ; Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoneda
authors.forename: Sachio
authors.initials: S
authors.lastname: Ito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kunisada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kanzaki
authors.forename: Aki
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics*; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000473:pathology*
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins; C587877:SS18-SSX1 fusion protein; C116512:SYT-SSX fusion protein; C093962:synovial sarcoma X breakpoint proteins