FOXP2confers oncogenic effects in prostate cancer through activating MET signalling

Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found thatFOXP2is overexpressed in human prostate cancer cells and prostate tumors, but its expression is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. To date, little is known regarding the link ofFOXP2to prostate cancer. We observed that highFOXP2expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression ofFOXP2induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely,FOXP2knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression ofFOXP2in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression ofFOXP2aberrantly activates oncogenic MET signalling and inhibitors targeting MET signalling effectively reverts theFOXP2-induced oncogenic phenotype. Additionally, the novel recurrentFOXP2-CPED1fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data demonstrate for the first time thatFOXP2is an oncogene involved in tumorigenicity of prostate.