XB130 promotes proliferation and invasion of gastric cancer cells.

XB130 promotes proliferation and invasion of gastric cancer cells.
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XB130促进胃癌细胞增殖和侵袭

DOI:
10.1186/1479-5876-12-1
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发表时间:
2014-01-04
影响因子:
7.4
通讯作者:
Liao W
Liao W
中科院分区:
医学2区
文献类型:
--
作者:
Shi M;Zheng D;Sun L;Wang L;Lin L;Wu Y;Zhou M;Liao W;Liao Y;Zuo Q;Liao W

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研究背景据报道,XB 130在甲状腺癌、食管癌等多种细胞中表达,促进甲状腺癌细胞的增殖和侵袭。本研究采用MTT法、克隆形成法、BrdU掺入法、三维培养法、免疫组化法等方法,观察了XB 130在胃癌中的表达,并探讨了XB 130在胃癌发生、转移中的作用。免疫组织化学和免疫荧光。Western blot分析也进行了鉴定的潜在mechanisms involved.ResultsThe增殖,迁移,和侵袭的胃癌细胞系SGC 7901和MNK 45都显着抑制了使用小发夹RNA敲低XB 130。在异种移植模型中,shXB 130转染的GC细胞植入裸鼠后,肿瘤生长明显受到抑制。在XB 130敲低后,GC细胞表现出更多的上皮样表型,表明上皮-间质转化(EMT)过程受到抑制。此外,沉默XB 130降低了p-Akt/Akt的表达,上调了上皮标志物包括E-cadherin、α-catenin和β-catenin的表达,下调了间充质标志物包括纤连蛋白和波形蛋白的表达。与肿瘤转移相关的癌蛋白,如MMP 2,MMP 9和CD 44,表达也显着降低。ConclusionsThese研究结果表明,XB 130增强细胞的运动性和侵袭性,通过调节EMT样过程,而沉默XB 130在GC抑制肿瘤的发生和转移,这表明它可能是一个潜在的治疗靶点。
BackgroundXB130 has been reported to be expressed by various types of cells such as thyroid cancer and esophageal cancer cells, and it promotes the proliferation and invasion of thyroid cancer cells. Our previous study demonstrated that XB130 is also expressed in gastric cancer (GC), and that its expression is associated with the prognosis, but the role of XB130 in GC has not been well characterized.MethodsIn this study, we investigated the influence of XB130 on gastric tumorigenesis and metastasis in vivo and in vitro using the MTT assay, clonogenic assay, BrdU incorporation assay, 3D culture, immunohistochemistry and immunofluorescence. Western blot analysis was also performed to identify the potential mechanisms involved.ResultsThe proliferation, migration, and invasion of SGC7901 and MNK45 gastric adenocarcinoma cell lines were all significantly inhibited by knockdown of XB130 using small hairpin RNA. In a xenograft model, tumor growth was markedly inhibited after shXB130-transfected GC cells were implanted into nude mice. After XB130 knockdown, GC cells showed a more epithelial-like phenotype, suggesting an inhibition of the epithelial-mesenchymal transition (EMT) process. In addition, silencing of XB130 reduced the expression of p-Akt/Akt, upregulated expression of epithelial markers including E-cadherin, α-catenin and β-catenin, and downregulated mesenchymal markers including fibronectin and vimentin. Expression of oncoproteins related to tumor metastasis, such as MMP2, MMP9, and CD44, was also significantly reduced.ConclusionsThese findings indicate that XB130 enhances cell motility and invasiveness by modulating the EMT-like process, while silencing XB130 in GC suppresses tumorigenesis and metastasis, suggesting that it may be a potential therapeutic target.
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