PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition
PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition
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PIK3R3 通过 ZEB1 诱导上皮间质转化促进胰腺癌转移
DOI：
10.1159/000489382
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Miao, Yi
中科院分区：
文献类型：
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作者：
Peng, Yun-Peng;Zhu, Yi;Miao, Yi
背景/目标：PIK 3R 3是磷脂酰肌醇3-激酶（PI 3 K）的调节亚基，其在几种类型的癌症的转移中起重要作用。然而，PIK 3R 3是否能促进胰腺癌（PC）的转移仍不清楚。在这项研究中，我们表征了PIK 3R 3在PC转移中的作用及其潜在机制。研究方法：采用RT-PCR、Western blot、免疫荧光（IF）和免疫组化（IHC）等方法检测不同细胞系和组织中基因和蛋白的表达。为了评估PIK 3R 3的功能和相关机制，使用具有RNAi介导的敲低或过表达的细胞进行一系列体外和体内测定。结果如下：PIK 3R 3在胰腺癌组织中显著过表达，特别是在转移癌组织中，以及在胰腺癌细胞中。功能分析表明，PIK 3R 3的过表达或敲低可分别促进或抑制PC细胞在体外和体内的迁移和侵袭。进一步的机制研究表明，ERK 1/2-ZEB 1通路可能是PIK 3R 3诱导PC细胞迁移和侵袭的重要机制。结论：PIK 3R 3可能通过促进ZEB 1诱导的EMT而促进PC的转移，可能成为限制PC转移的潜在治疗靶点。
Background/Aims: PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) which plays an essential role in the metastasis of several types of cancer. However, whether PIK3R3 can promote the metastasis of pancreatic cancer (PC) is still unclear. In this study, we characterized the role of PIK3R3 in metastasis of PC and underlying potential mechanisms. Methods: RT-PCR, western blot, immunofluorescence (IF) and immunohistochemistry (IHC) were applied to investigate the expression of genes and proteins in different cell lines and tissues. To assess the function of PIK3R3 and related mechanisms, the cells with RNAi-mediated knockdown or overexpression were used to perform a series of in vitro and in vivo assays. Results: PIK3R3 was significantly overexpressed in pancreatic cancer tissues, especially in metastatic cancer tissues, as well as in pancreatic cancer cells. Functional assays suggested that overexpression or knockdown of PIK3R3 could respectively promote or suppress the migration and invasion of PC cells in vitro and in vivo. Further mechanism related studies demonstrated that ERK1/2-ZEB1 pathway-triggered epithelial-mesenchymal transition (EMT) might be responsible for the PIK3R3-induced PC cell migration and invasion. Conclusion: PIK3R3 could promote the metastasis of PC by facilitating ZEB1 induced EMT, and could act as a potential therapeutic target to limit PC metastasis.