Polycystin-1 induces activation of the PI3K/AKT/mTOR pathway and promotes angiogenesis in renal cell carcinoma
Polycystin-1 induces activation of the PI3K/AKT/mTOR pathway and promotes angiogenesis in renal cell carcinoma
复制标题
多囊蛋白-1激活PI 3 K/AKT/mTOR通路促进肾细胞癌血管生成
DOI：
10.1016/j.canlet.2020.06.016
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发表时间：
2020-10-01
期刊：
影响因子：
9.7
通讯作者：
Korkolopoulou, Penelope
中科院分区：
文献类型：
--
作者：
Gargalionis, Antonios N.;Sarlani, Eleni;Korkolopoulou, Penelope
在本研究中，我们研究了机械敏感性多囊蛋白在肾癌中的表达及其功能作用。在115例肾癌患者中，我们检测了多囊蛋白-1(PC1)、多囊蛋白-2(PC2)、血管内皮生长因子(VEGF)和PI3K/Akt/mTOR信号通路的蛋白成分的表达，它们与肾癌和多囊肾疾病密切相关。与邻近正常组织相比，PC1和PC2在整个肾癌组织中的表达减少。当PC1和PC2分别与较高的分级和较低的5年生存率相关时，PC1和PC2显示高表达。PC1和PC2与PI3K的p110γ亚基呈正相关，高表达PC1的细胞倾向于Akt的激活/磷酸化。PC1和血管内皮生长因子的表达也呈正相关，而在IV期癌中，PC1增强了肿瘤的微血管网络。在人肾癌细胞中，PC1的功能抑制导致PI3K/Akt/mTOR通路上调，促进细胞增殖，抑制细胞迁移。结论，PC1调节异常与肾癌组织中血管生成增加和晚期疾病的特征有关。
In the present study we investigated the expression and the functional role of mechanosensitive polycystins in renal cell carcinoma (RCC). In 115 RCC patients we evaluated the protein expression of polycystin-1 (PC1), polycystin-2 (PC2), VEGF and protein components of the PI3K/Akt/mTOR pathway, which have been implicated both in RCC and polycystic kidney disease. PC1 and PC2 demonstrated reduced expression throughout the RCC tissue compared to the adjacent normal tissue. PC1 and PC2 revealed high expression when they were associated with higher grade and decreased 5-year survival respectively. PC1 and PC2 were positively correlated with p110 gamma subunit of PI3K and high PC1 expressing cells tended to display activation/phosphorylation of Akt. There was also a positive association between PC1 and VEGF expression, whereas PC1 augmented the tumor's microvascular network in stage IV carcinomas. In human RCC cells, functional inhibition of PC1 resulted in upregulation of the PI3K/Akt/mTOR pathway, enhanced cell proliferation and led to inhibition of cell migration. Conclusively, aberrant PC1 regulation is associated with increased angiogenesis and features of advanced disease in RCC tissues.