title: Prostaglandin E2 promotes hepatocellular carcinoma cell invasion through upregulation of YB-1 protein expression.
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.
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Shanyu
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Ma
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Yipin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Rong
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Shukai
authors.initials: S
authors.lastname: Xia
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Mingzhan
authors.initials: M
authors.lastname: Du
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shi
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Qinyi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Bai
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Leng
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D051840:Y-Box-Binding Protein 1 / Q000096:biosynthesis*
chemical_list: D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D015232:Dinoprostone