Rap2a serves as a potential prognostic indicator of renal cell carcinoma and promotes its migration and invasion through up-regulating p-Akt.

Rap2a serves as a potential prognostic indicator of renal cell carcinoma and promotes its migration and invasion through up-regulating p-Akt.
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Rap2a 作为肾细胞癌的潜在预后指标,通过上调 p-Akt 促进肾细胞癌的迁移和侵袭

DOI:
10.1038/s41598-017-06162-7
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发表时间:
2017-07-26
期刊:
影响因子:
4.6
通讯作者:
Pei DS
Pei DS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wu JX;Du WQ;Wang XC;Wei LL;Huo FC;Pan YJ;Wu XJ;Pei DS

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Rap2a是GTPase小超家族的成员,属于Ras超家族,其在癌症进展中的作用尚不清楚。我们前期的研究表明,Rap2a的异位表达增强了肺癌细胞的迁移和侵袭能力。然而,其在肾细胞癌(RCC)中的表达及分子机制尚未明确。本研究探讨Rap2a在人RCC中的临床意义及生物学功能。通过组织芯片免疫组化染色评估Rap2a在RCC中的临床意义。我们的数据显示,与正常肾组织相比,RCC组织中Rap2a的表达显著增加。Rap2a的异位表达增强了癌细胞的迁移和侵袭能力。相反,下调Rap2a抑制细胞侵袭。Rap2a对RCC细胞系的增殖无影响。同时,Rap2a可以调节体外Aktin的磷酸化水平。体内研究也表明,Rap2a正调控肾癌细胞的转移和p-Akt的表达。这些发现表明,Rap2a促进RCC转移,可能作为RCC预后的候选标志物和潜在的治疗靶点。
Rap2a, a member of the small GTPase superfamily, belongs to Ras superfamily, and its function in cancer progression is still poorly understood. Our previous study indicated that the ectopic expression of Rap2a enhanced the migration and invasion ability of lung cancer cells. However, its expression and molecular mechanism on renal cell carcinoma (RCC) have not been characterized. This study explored the clinical significance and biological function of Rap2a in human RCC. The clinical relevance of Rap2a in RCC was evaluated by immunohistochemical staining using tissue microarray. Our data showed that Rap2a expression was dramatically increased in RCC tissues compared with normal renal tissues. The ectopic expression of Rap2a enhanced the migration and invasive ability of cancer cells. In contrast, downregulation of Rap2a inhibited cell invasion. Rap2a had no effect on the proliferation of RCC cell lines. Meanwhile, Rap2a can regulate the phosphorylation level of Aktin vitro.In vivostudies also showed that Rap2a positively regulated metastasis of renal cancer cells and the expression of p-Akt. These findings indicate that Rap2a promotes RCC metastasis and may serve as a candidate RCC prognostic marker and a potential therapeutic target.
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