<i>FOXP2</i> confers oncogenic effects in prostate cancer.

Abstract

Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that <i>FOXP2</i> is 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. <i>FOXP2</i> is a FOX transcription factor family member and tightly associated with vocal development. To date, little is known regarding the link of <i>FOXP2</i> to prostate cancer. We observed that high <i>FOXP2</i> expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of <i>FOXP2</i> induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, <i>FOXP2</i> knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of <i>FOXP2</i> in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of <i>FOXP2</i> aberrantly activates oncogenic MET signaling and inhibition of MET signaling effectively reverts the <i>FOXP2</i>-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in <i>MET</i> and its associated gene <i>HGF</i>. Additionally, the novel recurrent <i>FOXP2-CPED1</i> fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data indicate that <i>FOXP2</i> is involved in tumorigenicity of prostate.