FOXP2 confers oncogenic effects in prostate cancer

  1. Xiaoquan Zhu  Is a corresponding author
  2. Chao Chen
  3. Dong Wei
  4. Yong Xu
  5. Siying Liang
  6. Wenlong Jia
  7. Jian Li
  8. Yanchun Qu
  9. Jianpo Zhai
  10. Yaoguang Zhang
  11. Pengjie Wu
  12. Qiang Hao
  13. Linlin Zhang
  14. Wei Zhang
  15. Xinyu Yang
  16. Lin Pan
  17. Ruomei Qi
  18. Yao Li
  19. Feiliang Wang
  20. Rui Yi
  21. Ze Yang  Is a corresponding author
  22. Jianye Wang  Is a corresponding author
  23. Yanyang Zhao  Is a corresponding author
  1. Beijing Hospital, China
  2. Peking University Shenzhen Hospital, China
  3. Second Hospital of Tianjin Medical University, China
  4. Qingdao Women and Children's Hospital, China
  5. City University of Hong Kong, China
  6. Beijing Jishuitan Hospital, China
  7. Beijing Tian Tan Hospital, China
  8. Harbin Medical University, China
  9. Peking University First Hospital, China
  10. China-Japan Friendship Hospital, China
  11. 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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Xiaoquan Zhu

    The Key Laboratory of Geriatrics, Beijing Hospital, Beijing, China
    For correspondence
    zhuxiaoquan3692@bjhmoh.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9099-5835
  2. Chao Chen

    Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Dong Wei

    Department of Urology, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yong Xu

    Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Siying Liang

    Genetic Testing Center, Qingdao Women and Children's Hospital, Qingdao, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Wenlong Jia

    Department of Computer Science, City University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Jian Li

    The Key Laboratory of Geriatrics, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Yanchun Qu

    Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Jianpo Zhai

    Department of Urology, Beijing Jishuitan Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Yaoguang Zhang

    Department of Urology, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Pengjie Wu

    Department of Urology, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Qiang Hao

    Department of Urology, Beijing Tian Tan Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Linlin Zhang

    School of Nursing, Harbin Medical University, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Wei Zhang

    Department of Pathology, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Xinyu Yang

    Department of Urology, Peking University First Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  16. Lin Pan

    China-Japan Friendship Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  17. Ruomei Qi

    The Key Laboratory of Geriatrics, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  18. Yao Li

    Department of Surgery, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  19. Feiliang Wang

    Department of Ultrasonography, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  20. Rui Yi

    The Key Laboratory of Geriatrics, Beijing Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  21. Ze Yang

    The Key Laboratory of Geriatrics, Beijing Hospital, Beijing, China
    For correspondence
    yangze2806@bjhmoh.cn
    Competing interests
    The authors declare that no competing interests exist.
  22. Jianye Wang

    Department of Urology, Beijing Hospital, Beijing, China
    For correspondence
    wangjy@bjhmoh.cn
    Competing interests
    The authors declare that no competing interests exist.
  23. Yanyang Zhao

    The Key Laboratory of Geriatrics, Beijing Hospitalpital, Beijing, China
    For correspondence
    zhaoyanyang3967@bjhmoh.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5139-5311

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.

Reviewing Editor

  1. Wilbert Zwart, Netherlands Cancer Institute, Netherlands

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.

Version history

  1. Received: June 21, 2022
  2. Preprint posted: July 6, 2022 (view preprint)
  3. Accepted: September 5, 2023
  4. Accepted Manuscript published: September 5, 2023 (version 1)
  5. 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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  1. Xiaoquan Zhu
  2. Chao Chen
  3. Dong Wei
  4. Yong Xu
  5. Siying Liang
  6. Wenlong Jia
  7. Jian Li
  8. Yanchun Qu
  9. Jianpo Zhai
  10. Yaoguang Zhang
  11. Pengjie Wu
  12. Qiang Hao
  13. Linlin Zhang
  14. Wei Zhang
  15. Xinyu Yang
  16. Lin Pan
  17. Ruomei Qi
  18. Yao Li
  19. Feiliang Wang
  20. Rui Yi
  21. Ze Yang
  22. Jianye Wang
  23. Yanyang Zhao
(2023)
FOXP2 confers oncogenic effects in prostate cancer
eLife 12:e81258.
https://doi.org/10.7554/eLife.81258

Share this article

https://doi.org/10.7554/eLife.81258

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