FOXP2 confers oncogenic effects in prostate cancer
- Beijing Hospital, China
- Peking University Shenzhen Hospital, China
- Second Hospital of Tianjin Medical University, China
- Qingdao Women and Children's Hospital, China
- City University of Hong Kong, China
- Beijing Jishuitan Hospital, China
- Beijing Tian Tan Hospital, China
- Harbin Medical University, China
- Peking University First Hospital, China
- China-Japan Friendship Hospital, China
- Beijing Hospitalpital, China
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. 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 signalling and inhibition of MET signalling 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.
Data availability
The RNA-Seq data from 10 pairs of primary prostate tumors and normal tissues has been deposited in GEO database with the accessions codes: GSE114740. The Whole Genome Sequencing data from FOXP2-CPED1 fusion-positive tumor (PC_1) has been deposited in SRA database with the accessions: SRR7223723.
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Expression profile of localized primary prostate cancer samples and the matched normal tissuesNCBI Gene Expression Omnibus, GSE114740.
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Studies of driver genes in prostate cancerNCBI Sequence Read Archive, SRR7223723.
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RNAseq Analysis of Formalin-Fixed Paraffin-Embedded Prostate Cancer TissuesNCBI Gene Expression Omnibus, GSE54460.
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Integrative genomic profiling of human prostate cancerNCBI Gene Expression Omnibus, GSE21032.
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The long tail of oncogenic drivers in prostate cancercBioPortal, doi: 10.1038/s41588-018-0078-z.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81872096)
- Xiaoquan Zhu
National Natural Science Foundation of China (81541152)
- Yanyang Zhao
National Natural Science Foundation of China (81472408)
- Jianye Wang
National Natural Science Foundation of China (81570789)
- Jian Li
Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2021-I2M-1-050)
- Yanyang Zhao
Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2018-I2M-1-002)
- Yanyang Zhao
12th 5-year National Program from the Ministry of Scientific Technology (2012BAI10B01)
- Ze Yang
- Jianye Wang
973 program grants from the National Basic Research Program of China (2014CB910503)
- Jian Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Institutional Animal Care and Use Committee of National Institute of Biological Sciences. All of the animals were handled according to the protocol approved by the Committee of National Institute of Biological Sciences, Beijing (Beijing, China). All surgery was performed under sodium pentobarbital anesthesia to minimize suffering.
Human subjects: This study was conducted in line with the Declaration of Helsinki and the study protocol was approved by the Research Ethics Board of the Beijing Hospital, National Health Commission (2015BJYYEC-101-01). All participants provided written informed consent before participation.
Reviewing Editor
- Wilbert Zwart, Netherlands Cancer Institute, Netherlands
Version history
- Received: June 21, 2022
- Preprint posted: July 6, 2022 (view preprint)
- Accepted: September 5, 2023
- Accepted Manuscript published: September 5, 2023 (version 1)
- Version of Record published: September 21, 2023 (version 2)
Copyright
© 2023, Zhu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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FOXP2 confers oncogenic effects in prostate cancer
eLife 12:e81258.
https://doi.org/10.7554/eLife.81258
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