Mechanisms underlying regulation of Wnt signaling pathway against cancer stem-and glioma cells

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Reduced expression in immortalized cells/ Dikkofp-3(REIC/ DKK3, REIC), a tumor suppressor gene, has been investigated in gene therapy studies in various cancers. Elsewhere we first demonstrated that REIC was down-regulated in glioblastoma(GBM) cells, and that its over-expression with plasmid vector drastically inhibited their growth via activation of intrinsic apoptotic pathway. However, whether adenovirus-mediated overexpression of REIC(Ad-REIC) contributes to anti-tumor effect in glioma remain unclear. We performed this study to assess the applicability of Ad-REIC in GBM and to verify the molecular mechanisms underlying anti-tumor effect of Ad-REIC We first document that Ad-REIC effectively inhibited the growth of GBM in a time-and dose dependent manner and induced apoptosis. We also found that Ad-REIC reduced expression of Wnt proteins and its receptor LRP6 but not ROR2 Our data suggest that interfering the activation of both canonical-and non-canonical Wnt signaling pathway via overexpression of REIC contributes at least partly to suppress cell survival in GBM.