Prostaglandin E2 promotes hepatocellular carcinoma cell invasion through upregulation of YB-1 protein expression

Zhang,Hai; Cheng,Shanyu; Zhang,Min; Ma,Xiuping; Zhang,Li; Wang,Yipin; Rong,Rong; Ma,Juan; Xia,Shukai; Du,Mingzhan; Shi,Feng; Wang,Jie; Yang,Qinyi; Bai,Xiaoming; Leng,Jing

doi:10.3892/ijo.2013.2234

Prostaglandin E2 promotes hepatocellular carcinoma cell invasion through upregulation of YB-1 protein expression

Authors:
- Hai Zhang
- Shanyu Cheng
- Min Zhang
- Xiuping Ma
- Li Zhang
- Yipin Wang
- Rong Rong
- Juan Ma
- Shukai Xia
- Mingzhan Du
- Feng Shi
- Jie Wang
- Qinyi Yang
- Xiaoming Bai
- Jing Leng
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Affiliations: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China
Published online on: December 30, 2013 https://doi.org/10.3892/ijo.2013.2234
Pages: 769-780

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Abstract

Prostaglandin E2 (PGE2) has been implicated in hepatocellular carcinoma cell invasion. Recently, it was reported that Y box-binding protein 1 (YB-1) is closely correlated with malignancy. This study was designed to examine the mechanisms by which PGE2 increases YB-1 expression and promotes HCC cell invasion. PGE2 greatly enhanced HCC cell invasion through upregulation of the YB-1 protein, and the EP1 receptor is mainly responsible for this regulation. Src and EGFR were both activated by PGE2, which in turn increased the phosphorylation levels of p44/42 MAPK. Src, EGFR and p44/42 MAPK were all involved in PGE2-induced YB-1 expression. Chemical inhibitors and RNAi analysis all confirmed the role of mTOR complex 1 in YB-1 expression induced by PGE2. Furthermore, YB-1 was able to regulate the expression of a series of EMT-associated genes, which indicated that YB-1 could have the potential to control the epithelial-mesenchymal transition process in HCC cells. These findings reveal that PGE2 upregulated YB-1 expression through the EP1/Src/EGFR/p44/42 MAPK/mTOR pathway, which greatly enhanced HCC cell invasion. This study for the first time describes the mechanisms through which PGE2 regulates YB-1 expression and promotes HCC cell invasion.

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