Stable overexpression of Nup88 enhances HeLa cell migration through independent regulation of Kif7 and Gli1

Elevated expression of nucleoporin (Nup) 88 is often observed in various types of cancer and correlates with tumor grade. However, the underlying molecular mechanism by which Nup88 induces cancer malignancy remains unclear. The present study showed that stable overexpression of Nup88 in HeLa cells enhanced cell migration by modulating the expression of kinesin family member (Kif) 7 and glioma‑associated oncogene homolog (Gli) 1. The expression level of Kif7, a negative regulator of the Hedgehog (Hh) pathway acting through the processing of Gli2 and Gli3, was markedly reduced at both the mRNA and protein levels in Nup88 overexpressing HeLa cells. The reduced expression of Kif7 was restored by treatment with a DNA methylation inhibitor, suggesting epigenetic regulation. Co‑overexpression of a truncated Kif7 (514‑1343 aa), which possesses a large part of the Gli2 binding domain, suppressed the Nup88‑induced migration, suggesting that the downregulation of Kif7 contributed to the enhanced cell migration. In parallel, Gli1 expression was elevated through activation of the MEK‑ERK pathway and its knockdown markedly suppressed Nup88‑induced cell migration. Although both Kif7 and Gli1 are components of the Hh pathway, neither the knockdown of Kif7 nor the overexpression of Gli1 affected the expression of the other. Instead, the truncated Kif7 (514‑1343 aa) physically interacted with Gli1, suggesting that Kif7 suppressed enhanced migration by inhibiting Gli1 function. These findings revealed that Nup88 promotes cell migration by modulating the expression of Kif7 and Gli1, providing new insight into the mechanism of Nup88‑driven malignancy.