Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
Int J Oncol. 2014 Mar;44(3):769-80. doi: 10.3892/ijo.2013.2234. Epub 2013 Dec 30.
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.
前列腺素 E2（PGE2）已被牵涉到肝癌细胞的侵袭中。最近有报道称，Y 盒结合蛋白 1（YB-1）与恶性肿瘤密切相关。本研究旨在探讨 PGE2 增加 YB-1 表达并促进 HCC 细胞侵袭的机制。PGE2 通过上调 YB-1 蛋白极大地增强了 HCC 细胞的侵袭能力，而 EP1 受体主要负责这种调节。PGE2 激活了Src 和 EGFR，进而增加了 p44/42 MAPK 的磷酸化水平。Src、EGFR 和 p44/42 MAPK 均参与了 PGE2 诱导的 YB-1 表达。化学抑制剂和 RNAi 分析均证实 mTOR 复合物 1 在 PGE2 诱导的 YB-1 表达中起作用。此外，YB-1 能够调节一系列 EMT 相关基因的表达，这表明 YB-1 有可能控制 HCC 细胞中的上皮-间充质转化过程。这些发现表明，PGE2 通过 EP1/Src/EGFR/p44/42 MAPK/mTOR 通路上调 YB-1 表达，从而极大地增强了 HCC 细胞的侵袭。本研究首次描述了 PGE2 调节 YB-1 表达并促进 HCC 细胞侵袭的机制。
