Abstract
Elevated expression of the nucleoporin Nup88, a constituent of the nuclear pore complex, is seen in various types of malignant tumors, but whether this overexpression contributes to the malignant phenotype has yet to be determined. Here, we investigated the effect of the overexpression of Nup88 on the migration and invasion of cervical cancer HeLa cells. The overexpression of Nup88 promoted a slight but significant increase in both migration and invasion, whereas knockdown of Nup88 by RNA interference suppressed these phenotypes. The observed phenotypes in Nup88-overexpressing HeLa cells were not due to the progression of the epithelial-to-mesenchymal transition or activation of NF-κB, which are known to be important for cell migration and invasion. Instead, we identified an upregulation of matrix metalloproteinase-12 (MMP-12) at both the gene and protein levels in Nup88-overexpressing HeLa cells. Upregulation of MMP-12 protein by the overexpression of Nup88 was also observed in one other cervical cancer cell line and two prostate cancer cell lines but not 293 cells. Treatment with a selective inhibitor against MMP-12 enzymatic activity significantly suppressed the invasive ability of HeLa cells induced by Nup88 overexpression. Taken together, our results suggest that overexpression of Nup88 can stimulate malignant phenotypes including invasive ability, which is promoted by MMP-12 expression.
Highlights
Nuclear pore complexes (NPCs) are channels that penetrate the nuclear envelope to mediate the selective trafficking of macromolecules between the cytoplasm and the nucleus in eukaryotic cells
Our findings demonstrate that Nup88 contributes to the malignant phenotype via increased expression of matrix metalloproteinase-12 (MMP-12) in HeLa cells
We found that the overexpression of Nup88-green fluorescent protein (GFP) in HeLa cells slightly, but significantly, promoted migration as compared to control HeLa cells overexpressing GFP (Fig. 1c, d)
Summary
Nuclear pore complexes (NPCs) are channels that penetrate the nuclear envelope to mediate the selective trafficking of macromolecules between the cytoplasm and the nucleus in eukaryotic cells. The vertebrate NPC is made up of about 30 distinct proteins termed nucleoporins (Nups) (Cronshaw et al 2002). One-third of Nups comprise phenylalanine-glycine (FG)-rich repeats, which combine to form a meshwork in the center of the NPC. This meshwork serves as a physical barrier to limit the passive diffusion of macromolecules through the NPC. Nuclear transport receptors, or karyopherins, bind to NPC via these FGrepeats to modulate the selective transport of proteins and mRNAs. A variety of Nups have been well-characterized with respect to nuclear trafficking. Suggest that NPCs play additional roles in cellular processes, including cancer progression (Simon and Rout 2014; Snow and Paschal 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
