FOXP2 confers oncogenic effects in prostate cancer
- The Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China
- Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University, China
- The Hong Kong University of Science and Technology Medical Center, China
- Department of Urology, Beijing Hospital, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China
- Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, China
- Department of Urology, Second Hospital of Tianjing Medical University, China
- Genetic Testing Center, Qingdao Women and Children's Hospital, China
- Department of Computer Science, City University of Hong Kong, China
- Department of Urology, Beijing Jishuitan Hospital, China
- Department of Urology, Beijing Tian Tan Hospital, Capital Medical University, China
- School of Nursing, Harbin Medical University, China
- Department of Pathology, Beijing Hospital, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China
- Department of Urology, Peking University First Hospital, Institute of Urology, China
- Clinical Institute of China-Japan Friendship Hospital, China
- Department of Surgery, Beijing Hospital, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Science, China
- The Department of Ultrasonography, Beijing Hospital, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China
Figures
Figure 1 with 4 supplements
Oncogenic roles of FOXP2 in prostate cancer.
(A) FOXP2-CPED1 fusion gene identified in the prostate tumor of patient (PC_1) by RNA-seq. Top: schematic of chromosome 7 with the position and strand orientation indicated for the FOXP2 and CPED1 …
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Figure 1—source data 1
Uncropped blot for Figure 1I.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-data1-v2.zip
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Figure 1—source data 2
Uncropped blot for Figure 1N.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-data2-v2.zip
Figure 1—figure supplement 1
Identification of FOXP2-CPED1 fusion gene in human prostate tumors.
(A) FOXP2-CPED1-specific PCR from cDNA derived from the prostate tumors (PC_1, PC_11) and their matched normal tissues (NT_1, NT_11), respectively. Marker, DNA marker. (B) Upper panel: a schematic …
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Figure 1—figure supplement 1—source data 1
Uncropped gel for Figure 1—figure supplement 1A.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-figsupp1-data1-v2.zip
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Figure 1—figure supplement 1—source data 2
Uncropped gel for Figure 1—figure supplement 1B.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-figsupp1-data2-v2.zip
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Figure 1—figure supplement 1—source data 3
Uncropped blot for Figure 1—figure supplement 1G.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-figsupp1-data3-v2.zip
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Figure 1—figure supplement 1—source data 4
Uncropped blot for Figure 1—figure supplement 1K.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-figsupp1-data4-v2.zip
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Figure 1—figure supplement 1—source data 5
Uncropped blot for Figure 1—figure supplement 1L.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-figsupp1-data5-v2.zip
Figure 1—figure supplement 2
Oncogenic roles of FOXP2 in prostate cancer.
(A) Detection of FOXP2 protein expression levels in our primary prostatic adenocarcinoma (PCA) and the matched normal tissues (n = 20) and samples of benign prostatic hyperplasia (BPH) (n = 5) by …
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Figure 1—figure supplement 2—source data 1
Uncropped blot for Figure 1—figure supplement 2A.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-figsupp2-data1-v2.zip
Figure 1—figure supplement 3
Oncogenic roles of FOXP2 in prostate cancer.
(A) Alignment of homologs of human FOXP2 and mouse Foxp2 showing high conservation between the two species. (B) Protein blot showing ectopic expression of FOXP2 and FOXP2-CPED1 fusion protein in …
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Figure 1—figure supplement 3—source data 1
Uncropped blot for Figure 1—figure supplement 3B.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig1-figsupp3-data1-v2.zip
Figure 1—figure supplement 4
Clinical significance of FOXP2 expression and its copy number alterations (CNAs) in prostate cancer.
(A) The relationship of FOXP2 expression with Gleason score (≥9) in 491 primary prostate cancer samples from the TCGA dataset (Prostate Adenocarcinoma, Provisional) (FOXP2-positive expression, n = …
Figure 2 with 1 supplement
FOXP2 activates oncogenic MET signaling in FOXP2-overexpressing cells and prostate tumors.
(A) Schematic indicating the analysis of the TCGA dataset (Prostate Adenocarcinoma, Provisional, n = 495). In total, n = 255, top 25%, high expression (n = 120), bottom 25%, low expression (n = …
Figure 2—figure supplement 1
FOXP2 activates oncogenic MET signaling in FOXP2-overexpressing cells.
(A) Gene expression heat map of the significantly upregulated and downregulated genes from RNA sequencing analysis of NIH3T3 cells overexpressing FOXP2 or FOXP2-CPED1 relative to control cells. …
Figure 3 with 1 supplement
Targeting MET signaling inhibits FOXP2-induced oncogenic effects.
(A) Immunoblotting of the expression levels of p-Met (Y1234/1235) and p-Akt (S473) in NIH3T3 cells overexpressing FOXP2 or FOXP2-CPED1 (left) or in RWPE-1 cells overexpressing FOXP2 or FOXP2-CPED1 …
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Figure 3—source data 1
Uncropped blot for Figure 3A.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig3-data1-v2.zip
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Figure 3—source data 2
Uncropped blot for Figure 3B.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig3-data2-v2.zip
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Figure 3—source data 3
Uncropped blot for Figure 3C.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig3-data3-v2.zip
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Figure 3—source data 4
Uncropped blot for Figure 3F.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig3-data4-v2.zip
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Figure 3—source data 5
Uncropped blot for Figure 3G.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig3-data5-v2.zip
Figure 3—figure supplement 1
FOXP2 activates oncogenic MET signaling in FOXP2-overexpressing cells.
(A) Protein blot showing expression level of MET and AKT in RWPE-1 cells stably expressing FOXP2 or FOXP2-CPED1 treated with the control siRNA and siMET. Relative ratios of the intensities of the …
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Figure 3—figure supplement 1—source data 1
Uncropped blot for Figure 3—figure supplement 1A.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig3-figsupp1-data1-v2.zip
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Figure 3—figure supplement 1—source data 2
Uncropped blot for Figure 3—figure supplement 1B.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig3-figsupp1-data2-v2.zip
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Figure 3—figure supplement 1—source data 3
Uncropped gel for Figure 3—figure supplement 1D.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig3-figsupp1-data3-v2.zip
Figure 4 with 1 supplement
Prostate-specific overexpression of FOXP2 causes prostatic intraepithelial neoplasia.
(A) Histological images of prostatic intraepithelial neoplasia in ARR2PB-FOXP2 or ARR2PB-FOXP2-CPED1 mice (×200) compared to wild-type control (×40) (mice 14 mo of age). A bar graph showing the …
Figure 4—figure supplement 1
Generation of transgenic mice with prostate-specific expression of FOXP2 or FOPX2-CPED1.
(A) Schematic of the FOXP2 and FOPX2-CPED1 transgene constructs with a composite ARR2PB promoter and a hGH_PA_terminator. Identification of ARR2PB-FOXP2 or ARR2PB-FOXP2-CPED1 transgenic mice at …
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Figure 4—figure supplement 1—source data 1
Uncropped gel for Figure 4—figure supplement 1C.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig4-figsupp1-data1-v2.zip
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Figure 4—figure supplement 1—source data 2
Uncropped blot for Figure 4—figure supplement 1D.
- https://cdn.elifesciences.org/articles/81258/elife-81258-fig4-figsupp1-data2-v2.zip
Author response image 1
A CellTiter-Glo assay was used to test the growth of HEK293 cells treated with the control siRNA and siFOXP2 (#2 5’- TGGACAGTCTTCAGTTCTA-3’, #3 5’-CCACCAATAACTCATCATT-3’) over a fourpoint time course.
Experiments were performed in triplicate and repeated five times with similar results. Inset, Protein blot showing knockdown of FOXP2 protein in cells. *P < 0.05 and **P < 0.01 by the MannWhitney U …
Author response image 2
Methylation status of FOXP2 gene in tumors from COSMIC datasets.
Author response image 3
Celltiter-Glo assay showed that HA-tagged MET overexpression was able to partially rescue the cell growth of PC3 prostate cancer cells stably expressing FOXP2 shRNA (two clones, #21 and #23).
P values calculated by the Mann-Whitney U test, mean ± s.d.; n = 4. Immunoblot showing ectopic expression of HA-tagged MET protein in PC3 cells stably expressing FOXP2 shRNA.
Additional files
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MDAR checklist
- https://cdn.elifesciences.org/articles/81258/elife-81258-mdarchecklist1-v2.pdf
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Supplementary file 1
Details of the clinical information of the samples by RNA-seq, the fusion genes identified in this study, the gene set enrichment analyses conducted, the transgenic mouse prostates examined, and the primers used.
- https://cdn.elifesciences.org/articles/81258/elife-81258-supp1-v2.docx
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Supplementary file 2
Correlation analyses in this study.
- https://cdn.elifesciences.org/articles/81258/elife-81258-supp2-v2.xlsx
