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载脂蛋白E2通过激活ERK1/2信号通路促进胰腺癌细胞的迁移和侵袭。

Apolipoprotein E2 Promotes the Migration and Invasion of Pancreatic Cancer Cells via Activation of the ERK1/2 Signaling Pathway.

作者信息

Wang Hui, Du Shaoxia, Cai Jun, Wang Juan, Shen Xiaohong

机构信息

School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Dec 22;12:13161-13171. doi: 10.2147/CMAR.S284115. eCollection 2020.

Abstract

BACKGROUND

Apolipoprotein E2 (ApoE2) is reported to be essential for cell metastasis and proliferation and has been considered a potential diagnostic marker in many cancers. However, the function of ApoE2 in the metastasis of pancreatic cancer, as well as the underlying mechanism, remain unclear.

PURPOSE

In this study, we explored the effect of ApoE2 on the migration and invasion abilities of pancreatic cancer cells and explored the underlying molecular mechanism.

METHODS AND RESULTS

Wound healing and Matrigel Transwell assays were used to investigate the role of ApoE2 in cell migration and invasion. Western blotting analysis showed that ApoE2 was overexpressed in pancreatic cancer tissues. Additionally, the overexpression of ApoE2 promoted the process of epithelial-mesenchymal transition (EMT) and enhanced the expression of MMP-2/9 in pancreatic cancer cells. Mechanistically, we found that inhibition of ERK1/2 signaling with PD98059 impaired the ApoE2-mediated promotion of cell migration, invasion and EMT.

CONCLUSION

This study demonstrated that ApoE2/ERK1/2 signaling promoted the migration and invasion of pancreatic cancer cells. ApoE2 might be a potential therapeutic target for the treatment of pancreatic cancer metastasis.

摘要

背景

据报道,载脂蛋白E2(ApoE2)对细胞转移和增殖至关重要,并且在许多癌症中被视为一种潜在的诊断标志物。然而,ApoE2在胰腺癌转移中的作用及其潜在机制仍不清楚。

目的

在本研究中,我们探讨了ApoE2对胰腺癌细胞迁移和侵袭能力的影响,并探究其潜在的分子机制。

方法与结果

采用伤口愈合实验和基质胶Transwell实验研究ApoE2在细胞迁移和侵袭中的作用。蛋白质印迹分析表明,ApoE2在胰腺癌组织中过表达。此外,ApoE2的过表达促进了上皮-间质转化(EMT)过程,并增强了胰腺癌细胞中MMP-2/9的表达。机制上,我们发现用PD98059抑制ERK1/2信号会削弱ApoE2介导的细胞迁移、侵袭和EMT促进作用。

结论

本研究表明,ApoE2/ERK1/2信号促进了胰腺癌细胞的迁移和侵袭。ApoE2可能是治疗胰腺癌转移的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1005/7764636/a561538c625b/CMAR-12-13161-g0001.jpg

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