uman Prostate Cancer Cells

Downloa RSS2-ERG and other gene fusions involving ETS factors and genes with strong promoter elements are on in prostate cancer. Although ERG activation has been linked to invasive properties of prostate canhe precise mechanisms and pathways of ERG-mediated oncogenesis remain poorly understood. Here, we that ERG knockdown in VCaP prostate cancer cells causes an activation of cell adhesion, resulting in ly induced active β1-integrin and E-cadherin expression as well as changes in WNT signaling. These ations were corroborated by data from ERG-overexpressing nontransformed prostate epithelial cells l as gene expression data from clinical prostate cancer samples, which both indicated a link between nd epithelial-to-mesenchymal transition (EMT). Upregulation of several WNT pathway members was ERG-positive prostate cancers, with frizzled-4 (FZD4) showing the strongest overexpression as verified h reverse transcription-PCR and immunostaining. Both ERG knockin and knockdown modulated the of FZD4 expression. FZD4 silencing could mimic the ERG knockdown phenotype by inducing active egrin and E-cadherin expression, whereas FZD4 overexpression reversed the phenotypic effects seen RG knockdown. Taken together, our results provide mechanistic insights to ERG oncogenesis in prostate with E cancer, involving activation of WNT signaling through FZD4, leading to cancer-promoting phenotypic effects, including EMT and loss of cell adhesion. Cancer Res; 70(17); 6735–45. ©2010 AACR.