Rab11a Is Overexpressed in Gastric Cancer and Regulates FAK/AKT Signaling.
Rab11a Is Overexpressed in Gastric Cancer and Regulates FAK/AKT Signaling.
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Rab11a 在胃癌中过度表达并调节 FAK/AKT 信号传导
DOI：
10.1155/2020/3494396
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发表时间：
2020
影响因子：
--
通讯作者：
Dong Q
中科院分区：
文献类型：
--
作者：
Du J;Fu L;Hao J;Lin X;Dong Q
Rab 11 a的失调与几种癌症的进展有关。然而，还没有针对人类胃癌的此类研究。在本研究中，我们检测了Rab 11 a蛋白的表达，发现它在108例胃癌组织中的49例中表达上调，并与局部浸润、淋巴结转移和晚期相关。Rab 11 a蛋白在胃癌细胞株中表达明显高于正常胃细胞株。我们将Rab 11 a质粒和siRNA转染到MGC 803和AGS细胞系中。Rab 11 a过表达增加了MGC 803和AGS细胞系的细胞生长速率、集落数和侵袭能力。使用siRNA下调Rab 11 a可降低细胞增殖率、集落数并抑制侵袭。Rab 11 a的过度表达也导致顺铂耐药。Annexin V/PI染色显示Rab 11 a过表达抑制顺铂诱导的细胞凋亡，而Rab 11 a缺失促进细胞凋亡。我们还发现Rab 11 a过表达维持线粒体膜电位。Western blot分析显示Rab 11 a增加MMP 2、cyclin D1、Bcl-2、p-FAK和p-AKT的蛋白表达，而Rab 11 a缺失则显示相反的作用。使用抑制剂阻断FAK下调Bcl-2，cyclin D1，MMP 2和p-AKT的表达，并消除Rab 11 a对这些蛋白的影响。总之，我们的数据表明Rab 11 a在人类胃癌中上调。Rab 11 a可能通过FAK/AKT信号通路促进细胞增殖和侵袭，以及顺铂敏感性和线粒体膜电位。
Dysregulation of Rab11a has been implicated in the progression of several cancers. However, there have been no such studies for human gastric cancers. In the current study, we examined Rab11a protein expression and found it was upregulated in 49 of 108 gastric cancer tissues and correlated with local invasion, nodal metastasis, and advanced stage. Rab11a protein was higher in gastric cancer cell lines than normal gastric cell line. We transfected Rab11a plasmid and siRNA in both MGC803 and AGS cell lines. Rab11a overexpression increased the cell growth rate, colony numbers, and invasion ability in both MGC803 and AGS cell lines. Downregulation of Rab11a using siRNA decreased the cell proliferation rate, colony numbers, and inhibited invasion. Rab11a overexpression also conferred cisplatin resistance. Annexin V/PI staining showed that Rab11a overexpression suppressed cisplatin-induced apoptosis, while Rab11a depletion promoted cell apoptosis. We also showed that Rab11a overexpression maintained mitochondrial membrane potential. Western blot analysis revealed that Rab11a increased protein expression of MMP2, cyclin D1, Bcl-2, p-FAK, and p-AKT, while Rab11a depletion showed the opposite effects. Blockage of FAK using inhibitor downregulated Bcl-2, cyclin D1, MMP2, and p-AKT expression and abolished the effects of Rab11a on these proteins. In summary, our data demonstrated that Rab11a is upregulated in human gastric cancers. Rab11a facilitated cell proliferation and invasion, as well as cisplatin sensitivity and mitochondrial membrane potential, possibly via the FAK/AKT signaling pathway.
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1038/nrgastro.2010.162
发表时间：
2010-11-01
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
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作者：
Nanda, Shreeya
通讯作者：
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