Nucleophosmin gene mutations promote NIH3T3 cell migration and invasion through CXCR4 and MMPs

Nucleophosmin (NPM1) plays key roles in ribosome biogenesis, centrosome duplication, and maintenance of genomic integrity. NPM1 mutations have been recently identified as the most frequent genetic alteration in acute myeloid leukemia and are related to leukemogenesis. NPM1 mutations are involved in the regulation of cell proliferation, cell cycle, and apoptosis. However, the oncogenic potential of NPM1 mutations is not fully understood. Here, we investigated the change of cell migration and invasion in vitro and the role of NPM1 mutations in this process. In our study, NIH3T3 cells were transfected with plasmids encoding NPM1 mutation A (NPM1 mA), and the cell chemotactic response in vitro was evaluated by cell migration and invasion assays. In addition, the expression levels of MMP-2, MMP-9 and CXCR4 were assayed by quantitative real-time PCR and western blotting. Our findings suggested that the migration and invasion of NIH3T3 cells were significantly enhanced after transfection with NPM1 mA (p<0.01). Furthermore, there was greater expression of MMP-9 and CXCR4 (p<0.01), but a lower expression of MMP-2 in the NPM1 mA group. These results demonstrate that NPM1 mutations may promote cell migration and invasion in vitro, and MMP-9 and CXCR4 may be involved in the regulation of cell invasion. Thus, this study sheds new light on the effect of NPM1 mutations on leukemogenesis. (C) 2010 Elsevier Inc. All rights reserved.