Knockdown of astrocyte elevated gene-1 (AEG-1) in cervical cancer cells decreases their invasiveness, epithelial to mesenchymal transition, and chemoresistance

被引:40
作者
Liu, Xiangwen [1 ,2 ]
Wang, Degui [1 ]
Liu, Huiling [3 ]
Feng, Ying [4 ]
Zhu, Tianyuan [5 ]
Zhang, Lang [1 ]
Zhu, Bingdong [2 ]
Zhang, Ying [2 ,6 ]
机构
[1] Lanzhou Univ, Sch Basic Med Sci, Inst Anat & Histol & Embryol, Lanzhou 730000, Peoples R China
[2] Lanzhou Univ, Inst Pathogen Biol, Sch Basic Med Sci, Lanzhou 730000, Peoples R China
[3] Gansu Prov Peoples Hosp, Dept Obstet & Gynecol, Lanzhou, Peoples R China
[4] Lanzhou Univ, Hosp 1, Dept Pathol, Lanzhou 730000, Peoples R China
[5] Maternal & Child Hlth Care Hosp Lanzhou City, Hysteroscop Ctr, Lanzhou, Peoples R China
[6] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA
基金
中国国家自然科学基金;
关键词
astrocyte elevated gene-1; AEG-1; chemoresistance; epithelial to mesenchymal transition; invasiveness; metastasis; cervical cancer; NF-KAPPA-B; STEM-CELLS; PROGRESSION; INVASION; METASTASIS; CADHERIN; PATHWAY; PROTEIN; ACTIVATION; METADHERIN;
D O I
10.4161/cc.28607
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During cancer development, epithelial-mesenchymal transition (EMT) facilitates tumor dissemination and metastatic spread, which is characterized by morphologic changes from epithelial cells to fibroblast-like cells, disassembly of intercellular junction, and increased cell motility. Overexpression of astrocyte elevated gene-1(AEG-1) in various cancer cell lines and cancers has been found to be associated with aggressive tumor behavior. We found that AEG-1 expression was elevated in low differentiation cervical cancer specimens from patients. However, little is known about the AEG-1's precise role in invasion and metastasis. Here we demonstrate that downregulation of AEG-1 by RNAi significantly decreased the invasion and migration of cervical cancer cells, suggesting that AEG-1 overexpression may enhance cancer cell motility by inducing EMT. Downregulation of AEG-1 also led to reduced expression of mesenchymal marker vimentin and the transcription factor Snail but upregulation of epithelial marker E-cadherin in HeLa cells. In addition, knockdown of AEG-1 decreased colony forming units and increased sensitivity to cancer drugs in vitro. Taken together, our results suggest that knockdown of AEG-1 could decrease EMT and chemoresistance in cervical cancer cells and attenuate their aggressive behavior.
引用
收藏
页码:1702 / 1707
页数:6
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