SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with poor prognosis.
SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with poor prognosis.
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DOI：
10.1186/s13046-017-0616-z
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发表时间：
2017-10-11
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Peng C;Zhao H;Song Y;Chen W;Wang X;Liu X;Zhang C;Zhao J;Li J;Cheng G;Wu D;Gao C;Wang X
我们以前的研究报道了SHC SH 2-domain binding protein 1（SHCBP 1）作为一种癌基因通过促进滑膜肉瘤（SS）细胞的增殖而发挥作用。然而，SHCBP 1是否对肿瘤转移有任何影响仍有待研究。采用免疫组化和实时荧光定量RT-PCR方法检测76例SS组织和2株SS细胞系中SHCBP 1的表达。探讨SHCBP 1表达与SS临床病理特征的关系。通过粘附、伤口愈合、Transwell和Matrigel管形成试验，探讨SHCBP 1在SS细胞粘附、迁移、侵袭和血管生成中的作用。Western blotting检测TGF-β1/Smad信号通路及EMT相关标志物的蛋白表达。免疫组化法检测肿瘤组织中与迁移、侵袭和EMT相关的关键分子。在目前的研究中，我们证明SHCBP 1过表达显着增强SS细胞的粘附，迁移，侵袭和血管生成。相反，SHCBP 1敲低在体外引起对这些表型的相反作用。SHCBP 1通过诱导SS细胞上皮间质转化（EMT）促进肿瘤转移。SHCBP 1基因敲低可阻断SS细胞的转移和EMT。此外，转化生长因子β1（TGF-β1）诱导SHCBP 1表达呈时间依赖性，SHCBP 1敲低可抑制TGF-β1诱导的EMT。TGF-β1/Smad信号通路的激活参与了SHCBP 1在SS中的致癌作用。此外，SS患者中SHCBP 1的高表达与肿瘤进展和生存率降低以及预后不良相关。以上结果提示，SHCBP 1可能通过靶向TGF-β1/Smad信号通路诱导EMT，从而促进SS的转移，有望成为SS治疗的潜在分子靶点。
Our previous studies reported that SHC SH2-domain binding protein 1 (SHCBP1) functions as an oncogene via promoting cell proliferations in synovial sarcoma (SS) cells. However, whether SHCBP1 has any effect on tumor metastasis remains unexplored. The expression of SHCBP1 was analyzed in 76 SS tissues and two SS cell lines by immunohistochemistry and real-time RT-PCR. The relationship between SHCBP1 expression and the clinicopathological features of SS was investigated. The role of SHCBP1 in SS cell adhesion, migration, invasion and angiogenesis was explored by adhesion, Wound healing, Transwell, and Matrigel tube formation assays. Western blotting was conducted to detect the protein expressions of TGF-β1/Smad signaling pathway and EMT-related markers. The key molecules associated with migration, invasion and EMT were evaluated by immunohistochemistry in tumor specimens. In current study, we demonstrated that SHCBP1 overexpression significantly enhanced adhesion, migration, invasion and angiogenesis of SS cells. In contrast, SHCBP1 knockdown elicited the opposite effects on these phenotypes in vitro. SHCBP1 promoted tumor metastasis through inducing epithelial-mesenchymal transition (EMT) in SS cells. SHCBP1 knockdown could block the incidence of metastasis and EMT in SS cells. Furthermore, transforming growth factor-β1 (TGF-β1) induced SHCBP1 expression in a time-dependent pattern and SHCBP1 knockdown inhibited TGF-β1-induced EMT. The activation of the TGF-β1/Smad signaling pathway was involved in the oncogenic functions of SHCBP1 in SS. In addition, high expression of SHCBP1 in SS patients was associated with tumor progression and decreased survival as well as poor prognosis. Taken together, our results indicate that SHCBP1 may promote the metastasis of SS by inducing EMT through targeting TGF-β1/Smad signaling pathway and can be a potential molecular target for SS therapy.
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SS18-SSX1下游靶基因SHCBP1的鉴定及其在滑膜肉瘤进展中的功能分析
影响因子：
--
作者：
Peng C;Zhao H;Chen W;Song Y;Wang X;Li J;Qiao Y;Wu D;Ma S;Wang X;Gao C
通讯作者：
Gao C
影响因子：
11.5
作者：
Fan, Yu;Shen, Bing;Liu, Yong
通讯作者：
Liu, Yong
影响因子：
45.3
作者：
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通讯作者：
Chibon, Frederic
影响因子：
11.2
作者：
Javelaud D;Alexaki VI;Dennler S;Mohammad KS;Guise TA;Mauviel A
通讯作者：
Mauviel A
DOI：
10.1083/jcb.201007060
发表时间：
2010-12-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Montembault E;Zhang W;Przewloka MR;Archambault V;Sevin EW;Laue ED;Glover DM;D'Avino PP
通讯作者：
D'Avino PP