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

被引:11
作者
Wang, Hui [1 ]
Du, Shaoxia [1 ]
Cai, Jun [1 ]
Wang, Juan [1 ]
Shen, Xiaohong [1 ]
机构
[1] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China
来源
CANCER MANAGEMENT AND RESEARCH | 2020年 / 12卷
关键词
apolipoprotein E2; ERK1/2; migration; invasion; pancreatic cancer; PROLIFERATION; DYSLIPIDEMIA; EMT; IDENTIFICATION; INHIBITION; EXPRESSION; SURVIVAL; APOE;
D O I
10.2147/CMAR.S284115
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:13161 / 13171
页数:11
相关论文
共 44 条
[1]  
[Anonymous], 2015, MED ONCOL, DOI DOI 10.1007/S12032-015-0547-541
[2]   Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1α-VEGF mediated angiogenesis [J].
Bai, Xueli ;
Zhi, Xiao ;
Zhang, Qi ;
Liang, Feng ;
Chen, Wei ;
Liang, Chao ;
Hu, Qida ;
Sun, Xu ;
Zhuang, Zhengping ;
Liang, Tingbo .
CANCER LETTERS, 2014, 355 (02) :281-287
[3]   Identification and characterization of a novel human aldose reductase-like gene [J].
Cao, DL ;
Fan, ST ;
Chung, SSM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (19) :11429-11435
[4]   Hypoxia induces TWIST-activated epithelial-mesenchymal transition and proliferation of pancreatic cancer cells in vitro and in nude mice [J].
Chen, Shi ;
Chen, Jiang-zhi ;
Zhang, Jia-qiang ;
Chen, Hui-xin ;
Yan, Mao-lin ;
Huang, Long ;
Tian, Yi-feng ;
Chen, Yan-lin ;
Wang, Yao-dong .
CANCER LETTERS, 2016, 383 (01) :73-84
[5]  
Chen YC, 2005, CANCER RES, V65, P331
[6]   Osteopontin Increases Migration and MMP-9 Up-Regulation Via αvβ3 Integrin, FAK, ERK, and NF-κB-Dependent Pathway in Human Chondrosarcoma Cells [J].
Chen, Ying-Ju ;
Wei, Ying-Ying ;
Chen, Hsien-Te ;
Fong, Yi-Chin ;
Hsu, Chin-Jung ;
Tsai, Chun-Hao ;
Hsu, Horng-Chaung ;
Liu, Shing-Hwa ;
Tang, Chih-Hsin .
JOURNAL OF CELLULAR PHYSIOLOGY, 2009, 221 (01) :98-108
[7]  
DALLONGEVILLE J, 1992, J LIPID RES, V33, P447
[8]   Apolipoprotein E2 modulates cell cycle function to promote proliferation in pancreatic cancer cells via regulation of the c-Myc-p21Waf1 signalling pathway [J].
Du, Shaoxia ;
Wang, Hui ;
Cai, Jun ;
Ren, Runling ;
Zhang, Wenwen ;
Wei, Wei ;
Shen, Xiaohong .
BIOCHEMISTRY AND CELL BIOLOGY, 2020, 98 (02) :191-202
[9]   Identification of ApoE as an autocrine/paracrine factor that stimulates neural stem cell survival via MAPK/ERK signaling pathway [J].
Gan, Hui Theng ;
Tham, Muly ;
Hariharan, Srivats ;
Ramasamy, Srinivas ;
Yu, Yuan Hong ;
Ahmed, Sohail .
JOURNAL OF NEUROCHEMISTRY, 2011, 117 (03) :565-578
[10]   GM-CSF enhances tumor invasion by elevated MMP-2,-9, and-26 expression [J].
Gutschalk, Claudia M. ;
Yanamandra, Archana K. ;
Linde, Nina ;
Meides, Alice ;
Depner, Sofia ;
Mueller, Margareta M. .
CANCER MEDICINE, 2013, 2 (02) :117-129