TY - JOUR
T1 - FOXP2 confers oncogenic effects in prostate cancer
AU - Zhu, Xiaoquan
AU - Chen, Chao
AU - Wei, Dong
AU - Xu, Yong
AU - Liang, Siying
AU - Jia, Wenlong
AU - Li, Jian
AU - Qu, Yanchun
AU - Zhai, Jianpo
AU - Zhang, Yaoguang
AU - Wu, Pengjie
AU - Hao, Qiang
AU - Zhang, Linlin
AU - Zhang, Wei
AU - Yang, Xinyu
AU - Pan, Lin
AU - Qi, Ruomei
AU - Li, Yao
AU - Wang, Feiliang
AU - Yi, Rui
AU - Yang, Ze
AU - Wang, Jianye
AU - Zhao, Yanyang
PY - 2023
Y1 - 2023
N2 - 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. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. 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 signaling and inhibition of MET signaling effectively reverts the FOXP2-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF. 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 indicate that FOXP2 is involved in tumorigenicity of prostate. © Zhu et al.
AB - 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. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. 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 signaling and inhibition of MET signaling effectively reverts the FOXP2-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF. 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 indicate that FOXP2 is involved in tumorigenicity of prostate. © Zhu et al.
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U2 - 10.7554/ELIFE.81258
DO - 10.7554/ELIFE.81258
M3 - RGC 21 - Publication in refereed journal
C2 - 37668356
SN - 2050-084X
VL - 12
JO - eLife
JF - eLife
M1 - e81258
ER -