Bai Xiao-Ming, Zhang Wei, Liu Ning-Bo, Jiang Hui, Lou Ke-Xin, Peng Tao, Ma Juan, Zhang Li, Zhang Hai, Leng Jing
Laboratory of Reproductive Medicine, Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, PR China.
Oncol Rep. 2009 Jan;21(1):129-36.
Prostaglandin E2 has been implicated in cell growth and metastasis in many types of cancers. However, the effects of PGE2 and its mechanism on cell adhesion, migration, and invasion have not been clarified yet. In this study, we found PGE2 treatment significantly increased the cell adhesion, migration, and invasion in hepatocellular carcinoma (HCC) cells. In addition, the effects of PGE2 were found to be associated with focal adhesion kinase (FAK). PGE2 treatment increased the phosphorylation and synthesis of FAK in a dose-dependent manner. RNA interference targeting FAK suppressed PGE2-mediated cell adhesion and migration. Furthermore, the downstream proteins of FAK, paxillin and Erk2, were also activated by PGE2. PGE2 treatment increased the phosphorylation and synthesis of paxillin in a dose-dependent manner. PGE2 treatment also induced the phosphorylation of Erk2. PD98059, the specific inhibitor of MEK, suppressed PGE2-mediated cell adhesion and migration. However, it had no effect on PGE2-induced activation and synthesis of FAK. These results demonstrated that PGE2 greatly induced HCC cell adhesion, migration, and invasion by activating FAK/paxillin/Erk pathway.
前列腺素E2已被证实与多种癌症的细胞生长和转移有关。然而，PGE2对细胞黏附、迁移和侵袭的影响及其机制尚未阐明。在本研究中，我们发现PGE2处理显著增加了肝癌（HCC）细胞的黏附、迁移和侵袭能力。此外，发现PGE2的作用与黏着斑激酶（FAK）有关。PGE2处理以剂量依赖的方式增加了FAK的磷酸化和合成。靶向FAK的RNA干扰抑制了PGE2介导的细胞黏附和迁移。此外，FAK的下游蛋白桩蛋白和Erk2也被PGE2激活。PGE2处理以剂量依赖的方式增加了桩蛋白的磷酸化和合成。PGE2处理还诱导了Erk2的磷酸化。MEK的特异性抑制剂PD98059抑制了PGE2介导的细胞黏附和迁移。然而，它对PGE2诱导的FAK激活和合成没有影响。这些结果表明，PGE2通过激活FAK/桩蛋白/Erk途径极大地诱导了肝癌细胞的黏附、迁移和侵袭。
