Sialidase Neu4L overexpression up-regulates wnt/beta catenin signaling in SK-N-BE neuroblastoma cells, promoting the propagation of malignant neuroblasts

Sialidase Neu4 has been recently discovered (1) and exists as two forms Neu4 long (Neu4L) and Neu4 short (Neu4S). We demonstrated that more aggressive neuroblastoma cell lines characteristically show a high expression of Neu4L and, on these bases, we investigated the significance of this peculiarity by stably over-expressing Neu4L in the human neuroblastoma cells SK-N-BE. Neu4L over-expression accelerated proliferation, as assessed by 3[H]thymidine incorporation (+30%), by cell count (+36%) and by MTT test (+40%). Moreover, Neu4L over-expressing cells were unable to differentiate under FBS depletion, as we assessed following the formation of neurites and src and N-CAM, as neuronal markers. These changes seem to be related to a marked activation of the Wnt/-catenin pathway demonstrated by the increase of active -catenin (+32%), β-catenin-TCF transcriptional activity (+52%), c-myc, cyclin D2, and axin2 expression. The direct substrates of Neu4L, in SK-N-BE cells are sialoglycoproteins in the range of 50 kDa; it could be hypothesized that one of these glycoproteins could belong to the Wnt family and that its functionality is strictly determined by its sialylation degree. Thus, Neu4L induces proliferation and enhances the self-renewal of neuroblasts promoting the activation of Wnt/-catenin signaling. 1) Monti E et al. (2004) Genomics 83: 445–53