Testes-specific protease 50 (TSP50) promotes invasion and metastasis by inducing EMT in gastric cancer.
Testes-specific protease 50 (TSP50) promotes invasion and metastasis by inducing EMT in gastric cancer.
复制标题
睾丸特异性蛋白酶 50 (TSP50) 通过诱导胃癌 EMT 促进侵袭和转移
DOI：
10.1186/s12885-018-4000-y
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发表时间：
2018-01-23
期刊：
影响因子：
3.8
通讯作者：
Xue L
中科院分区：
文献类型：
--
作者：
Cao QH;Liu F;Li CZ;Liu N;Shu M;Lin Y;Ding L;Xue L
据报道，tsp50（睾丸特异性蛋白酶50）是一种候选癌基因，在多种癌症中过表达。我们前期的研究表明，TSP50蛋白在胃癌中升高，其高表达与不良预后和淋巴结转移有关。然而，TSP50在胃癌中的作用尚不清楚。方法采用sqrt - pcr、western blot检测胃癌细胞株中TSP50的表达。通过BrdU掺入实验、细胞计数、伤口愈合和transwell实验检测TSP50在增殖和侵袭中的作用。采用免疫组织化学和western blot方法确定可能的机制。结果stsp50在大多数胃癌细胞系中mRNA和蛋白水平均高表达。胃癌细胞中上调TSP50可增强其增殖和侵袭性，而通过其特异性shRNA下调TSP50可降低其增殖和侵袭性。胃癌组织中TSP50与E-Cadherin呈负相关，两者联合应用有助于预测预后及淋巴结转移。机制研究表明，过表达TSP50增加了上皮-间质转化（EMT）标志物Vimentin和Twist的表达，降低了上皮标志物E-Cadherin的表达。NF-κB信号通路参与了TSP50对胃癌细胞EMT、迁移和侵袭的调控作用。结论tsp50参与NF-κB依赖性EMT激活，促进胃癌细胞增殖、迁移和侵袭。靶向TSP50可能为胃癌的治疗提供一种新的治疗策略。
BackgroundTSP50 (testes-specific protease 50) has been reported to be a candidate oncogene and is overexpressed in various cancers. Our previous study demonstrated that TSP50 protein is elevated in gastric cancer, and its high expression is associated with unfavorable prognosis and lymph node metastasis. However, the role of TSP50 in gastric cancer remains elusive.MethodsqRT-PCR, western blot were used to determine TSP50 expression in gastric cancer cell lines. Role of TSP50 in proliferation and invasion was examined by BrdU incorporation assay, cell count, wound healing and transwell assay. Immunohistochemistry and western blot were performed to identify the potential mechanisms involved.ResultsTSP50 was highly expressed in most of the gastric cancer cell lines at both mRNA and protein levels. Up-regulation of TSP50 in gastric cancer cells enhanced proliferation and invasiveness, whereas down-regulation of TSP50 by its specific shRNA decreased it. A negative correlation between TSP50 and E-Cadherin was found in gastric cancer tissues, and combination of them improves the prediction for prognosis and lymph node metastasis. Mechanistic studies revealed that overexpression of TSP50 increased the expression of epithelial-to-mesenchymal transition (EMT) markers including Vimentin, and Twist, and decreased the epithelial marker E-Cadherin. NF-κB signaling pathway is involved in the regulatory effects of TSP50 on EMT, migration and invasion in gastric cancer cells.ConclusionTSP50 promotes the proliferation, migration and invasion of gastric cancer cells involving NF-κB dependent EMT activation. Targeting TSP50 may provide a novel therapeutic strategy for the management of gastric cancer.
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影响因子：
4.1
作者：
Song, Zhen-Bo;Bao, Yong-Li;Li, Yu-Xin
通讯作者：
Li, Yu-Xin
影响因子：
10.5
作者：
Timmerman, LA;Grego-Bessa, J;de la Pompa, JL
通讯作者：
de la Pompa, JL
影响因子：
--
作者：
Liu F;Cao QH;Lu DJ;Luo B;Lu XF;Luo RC;Wang XG
通讯作者：
Wang XG
睾丸特异性蛋白酶 50 通过增加 NF-κB 依赖性基质金属蛋白酶 9 的表达来促进细胞侵袭和转移
影响因子：
9
作者：
通讯作者：
--
睾丸特异性蛋白酶50（TSP50）的过表达预测胃癌患者的预后不良。
影响因子：
2
作者：
Liu F;Cao Q;Liu N;Li C;You C;Liu C;Xue L;Luo R
通讯作者：
Luo R