Overall, accumulation of cytoplasmic β-catenin and downregulation of other Wnt pathway proteins (APC/Axin/DKK3/FRP2/WIF1) were found in approximately half of the breast cancers (47%) in our cohort.
Since gene silencing of certain Wnt antagonists was found to be correlated with adverse patient survival in cancer, we aimed at investigating a potential prognostic impact of the two Wnt antagonizing molecules WIF1 and DKK3 in breast cancer, which are frequently silenced by promoter methylation in this disease.
Our findings establish the WIF1 gene as a target for epigenetic silencing in breast cancer and provide a mechanistic link between the dysregulation of Wnt signaling and breast tumorigenesis.