FOXP2 confers oncogenic effects in prostate cancer through activating MET signalling

Zhu, X.; Chen, C.; Wei, D.; Xu, Y.; Liang, S.; Jia, W.; Li, J.; Qu, Y.; Zhai, J.; Zhang, Y.; Wu, P.; Hao, Q.; Zhang, L.; Zhang, W.; Yang, X.; Pan, L.; Qi, R.; Li, Y.; Wang, F.; Yi, R.; Yang, Z.; Wang, J.; Zhao, Y.

doi:10.1101/2022.07.06.498943

bioRxiv · 10.1101/2022.07.06.498943

FOXP2 confers oncogenic effects in prostate cancer through activating MET signalling

Zhu, X.·Chen, C.·Wei, D.·Xu, Y.·Liang, S.·Jia, W.·Li, J.·Qu, Y.·Zhai, J.·Zhang, Y.·Wu, P.·Hao, Q.·Zhang, L.·Zhang, W.·Yang, X.·Pan, L.·Qi, R.·Li, Y.·Wang, F.·Yi, R.·Yang, Z.·Wang, J.·Zhao, Y.

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Abstract

Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 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. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signalling and inhibitors targeting MET signalling effectively reverts the FOXP2-induced oncogenic phenotype. Additionally, the novel recurrent FOXP2-CPED1 fusion 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 that FOXP2 is an oncogene involved in tumorigenicity of prostate.

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Zhu, X., Chen, C., Wei, D., Xu, Y., Liang, S., Jia, W., Li, J., Qu, Y., Zhai, J., Zhang, Y., Wu, P., Hao, Q., Zhang, L., Zhang, W., Yang, X., Pan, L., Qi, R., Li, Y., Wang, F., Yi, R., Yang, Z., Wang, J., Zhao, Y.. 2022-07-06. FOXP2 confers oncogenic effects in prostate cancer through activating MET signalling. https://doi.org/10.1101/2022.07.06.498943

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