Truncated SSX protein suppresses synovial sarcoma cell proliferation by inhibiting the localization of SS18-SSX fusion protein.
Truncated SSX protein suppresses synovial sarcoma cell proliferation by inhibiting the localization of SS18-SSX fusion protein.
复制标题
截短的SSX蛋白通过抑制SS18-SSX融合蛋白的定位来抑制滑膜肉瘤细胞的增殖。
DOI：
10.1371/journal.pone.0077564
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ouchida M
中科院分区：
文献类型：
--
作者：
Yoneda Y;Ito S;Kunisada T;Morimoto Y;Kanzaki H;Yoshida A;Shimizu K;Ozaki T;Ouchida M
滑膜肉瘤是一种相对少见的高级别软组织肉瘤，多发生在年轻人四肢，可诱发肺部和淋巴结转移，预后不良。在滑膜肉瘤患者中，观察到t(X；18)(p11.2；q11.2)的特异性染色体易位，该易位表达的SS18-SSX融合蛋白被认为与发病有关。然而，该融合蛋白在滑膜肉瘤发病机制中的作用尚未完全阐明。在本研究中，我们重点研究了SS18-SSX融合蛋白的定位模式。我们构建了SS18-SSX全长、截短SS18部分(TSS18)和截短SSX部分(TSSX)的表达载体，并用荧光蛋白标记。将这些表达载体导入滑膜肉瘤SYO-1细胞，在荧光显微镜下观察这些蛋白的表达。SS18-SSX融合蛋白在细胞核内呈现典型的斑点模式。然而，当SS18-SSX与tSSX共表达时，SS18-SSX的定位模式从斑点模式转变为弥散模式，类似于tSSX和SSX的定位模式。此外，外源性tSSX的表达抑制了滑膜肉瘤SYO-1和YaFuSS细胞的增殖和集落形成。我们的结果表明SS18-SSX的斑点定位模式通过SS18-SSX融合蛋白的SSX部分与肿瘤的发生密切相关。这些发现可用于进一步了解滑膜肉瘤的发病机制，并为发展滑膜肉瘤的分子靶向治疗方法奠定基础。
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.
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影响因子：
3.7
作者：
Barco R;Garcia CB;Eid JE
通讯作者：
Eid JE
影响因子：
8
作者：
Lim, FL;Soulez, M;Knight, JC
通讯作者：
Knight, JC
影响因子：
11.2
作者：
de Bruijn, Diederik R. H.;Allander, Susanne V.;van Kessel, Ad Geurts
通讯作者：
van Kessel, Ad Geurts
影响因子：
3.5
作者：
Brodin, B;Haslam, K;Larsson, O
通讯作者：
Larsson, O
影响因子：
8
作者：
de Bruijn, DRH;dos Santos, NR;van Kessel, AG
通讯作者：
van Kessel, AG