Rap1A promotes ovarian cancer metastasis via activation of ERK/p38 and notch signaling.
Rap1A promotes ovarian cancer metastasis via activation of ERK/p38 and notch signaling.
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Rap1A 通过激活 ERK/p38 和 notch 信号促进卵巢癌转移
DOI：
10.1002/cam4.946
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发表时间：
2016-12
期刊：
影响因子：
4
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Lu L;Wang J;Wu Y;Wan P;Yang G
作为Ras相关蛋白之一，Rap 1A与癌症的发生和发展有关。然而，Rap 1A在卵巢癌中的确切功能仍不清楚。在这里，我们表明Rap 1A通过刺激细胞增殖，迁移和侵袭促进卵巢癌肿瘤的发生和转移在体内和体外。机制研究表明，Rap 1A激活细胞外信号调节激酶（ERK），p38丝裂原活化蛋白激酶（MAPK）和Notch途径，导致几种上皮间质转化（EMT）标志物如蛞蝓，zeb 1，波形蛋白，纤连蛋白和MMP 9的表达增强。然而，用Notch抑制剂DAPT或ERK抑制剂（U 0126）预处理Rap 1A过表达细胞可抑制这些分子的上调表达。这些发现首次提供了Rap 1A通过ERK/p38和Notch信号通路与卵巢癌发生发展相关的证据，表明Rap 1A可用作卵巢癌的新诊断标志物或治疗靶点。
As one of the Ras‐associated proteins, Rap1A has been linked to cancer initiation and development. However, the precise function of Rap1A in ovarian cancer is still not understood. Here, we show that Rap1A promotes ovarian cancer tumorigenesis and metastasis via stimulating cell proliferation, migration and invasion both in vivo and in vitro. Mechanistic study showed that Rap1A activates extracellular signal‐regulated kinase (ERK), p38 mitogen‐activated protein kinase (MAPK) and Notch pathways, leading to the enhanced expression of several epithelial‐mesenchymal transition (EMT) markers such as slug, zeb1, vimentin, fibronectin, and MMP9. However, the pretreatment of Rap1A‐overexpressing cells with the Notch inhibitor DAPT or ERK inhibitor (U0126) inhibited the up‐regulated expression of those molecules. These findings provide the first evidence linking Rap1A with ovarian cancer development through the ERK/p38 and Notch signaling pathways, indicating that Rap1A may be used as a novel diagnostic marker or a therapeutic target for ovarian cancer.