Li Xiao, Xu Dong-Hui, Liu Fan, Liu Guo-Yan, Lu Kun, Deng Xiao-Ling, Li Qi-Fu, Shi Song-Lin
Department of Basic Medicine, Medical College of Xiamen University/Cancer Research Center of Xiamen University, Xiamen, 361102, P.R. China.
Department of Hepatic Biliary Pancreatic Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian, P.R. China.
J Cell Biochem. 2017 Oct;118(10):3225-3236. doi: 10.1002/jcb.25971. Epub 2017 May 3.
Nucleophosmin(NPM), heavily implicated in diverse solid tumors, is an important multifunctional protein mainly located in the nucleolus. Our previous study confirmed that NPM can also localize and accumulate in the cytoplasm of liver cancer cells. However, the role of cytoplasmic NPM (NPMc +) is unclear. Here, we showed that both nucleolar NPM and NPMc+ could promote cell proliferation, although the effect of NPMc+ was weaker than that of NPM. Cell adhesion ability of hepatoma cells was significantly reduced to a greater extent by NPMc+ expression. Nucleolar NPM enhanced cell migration and invasion, whereas NPMc+ impeded cell migration and invasion. The investigation of NPM interactional proteins by proteomic method demonstrated that the NPM was involved in multiple biological processes. By contrast, the interactional proteins of NPMc+ were mainly implicated in tRNA amino acylation regulation. The interactional network of NPMc+ was significantly small and simple. These results suggested that relocation of NPM altered its interactional network and consequently disturbed the primary functions, including cell proliferation, adhesion, migration, and invasion. NPM plays a promotional role in cancer and the reducing relocation may be a potential therapeutic target for hepatocellular carcinoma. J. Cell. Biochem. 118: 3225-3236, 2017. © 2017 Wiley Periodicals, Inc.
核磷蛋白(NPM)与多种实体瘤密切相关,是一种主要位于核仁的重要多功能蛋白。我们之前的研究证实,NPM也可在肝癌细胞的细胞质中定位并积累。然而,细胞质NPM(NPMc +)的作用尚不清楚。在此,我们发现核仁NPM和NPMc +均可促进细胞增殖,尽管NPMc +的作用比NPM弱。NPMc +的表达可更显著地降低肝癌细胞的细胞黏附能力。核仁NPM增强细胞迁移和侵袭能力,而NPMc +则阻碍细胞迁移和侵袭。通过蛋白质组学方法对NPM相互作用蛋白的研究表明,NPM参与多种生物学过程。相比之下,NPMc +的相互作用蛋白主要涉及tRNA氨基酰化调节。NPMc +的相互作用网络明显更小且更简单。这些结果表明,NPM的重新定位改变了其相互作用网络,从而扰乱了包括细胞增殖、黏附、迁移和侵袭在内的主要功能。NPM在癌症中起促进作用,减少其重新定位可能是肝细胞癌的一个潜在治疗靶点。《细胞生物化学杂志》118: 3225 - 3236, 2017。© 2017威利期刊公司