FGFR3-TACC3 fusion gene promotes glioblastoma malignant progression through the activation of STAT3 signaling pathway
ObjectiveThe Fibroblast growth factor receptors 3-transforming acidic coiled-coil-containing protein 3 (FGFR3-TACC3, F3-T3) oncogenic fusion gene, identified in malignant tumors such as gliomas and bladder cancer, has been particularly noted in recurrent gliomas where it is considered to drive malig...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1560008/full |
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| author | Yiming Li Yiming Li Jianshen Liang Jianshen Liang Jianshen Liang Xiude Ren Xiude Ren Jiahe Guo Jiahe Guo Jiahe Guo Xisen Wang Xisen Wang Xisen Wang Xuya Wang Xuya Wang Xuya Wang Shengping Yu Shengping Yu Tao Li Tao Li Xuejun Yang Xuejun Yang Xuejun Yang |
| author_facet | Yiming Li Yiming Li Jianshen Liang Jianshen Liang Jianshen Liang Xiude Ren Xiude Ren Jiahe Guo Jiahe Guo Jiahe Guo Xisen Wang Xisen Wang Xisen Wang Xuya Wang Xuya Wang Xuya Wang Shengping Yu Shengping Yu Tao Li Tao Li Xuejun Yang Xuejun Yang Xuejun Yang |
| author_sort | Yiming Li |
| collection | DOAJ |
| description | ObjectiveThe Fibroblast growth factor receptors 3-transforming acidic coiled-coil-containing protein 3 (FGFR3-TACC3, F3-T3) oncogenic fusion gene, identified in malignant tumors such as gliomas and bladder cancer, has been particularly noted in recurrent gliomas where it is considered to drive malignant progression, thus presenting itself as a viable therapeutic target. However, the precise mechanism by which F3-T3 facilitates the malignant progression of glioma is not fully understood.MethodsCorrection analysis of STAT3 and FGFR3 with major glioma mutation types and pan-cancer analysis was conducted using The Cancer Genome Atlas (TCGA) database. A series of phenotypic experiments, including CCK-8, EdU, colony-formation assay, wound healing assay, and transwell assay were conducted to detect the effects of F3-T3 on proliferation, invasion, and migration of glioma cells. The association between F3-T3 and epithelial-mesenchymal transition (EMT) was investigated through enrichment analysis of the E-MTAB-6037 gene chip database and confirmed by western blot. The underling mechanism were further inferred and validated through RNA sequencing, E-MTAB-6037 gene chip data, and western blot. The relationship between p-STAT3 expression and the WHO grade of glioma was evaluated using immunohistochemistry (IHC) and tissue microarray analysis. Furthermore, the results of vivo experiments and IHC has confirmed the impact of F3-T3 on glioma malignant progression and activation of the STAT3 signaling pathway.ResultsThe experimental results from this study indicate that F3-T3 accelerates the epithelial-mesenchymal transition (EMT) process in glioma cells, thereby promoting their proliferation, invasion, and migration capabilities. Mechanistically, it was determined through RNA sequencing that the signal transducer and activator of transcription 3 (STAT3) signaling pathway is crucial for the malignant progression of F3-T3. This finding was further supported through follow-up experiments conducted after STAT3 knockdown. The role of the STAT3 pathway in gliomas was also reinforced through bioinformatic analysis and immunohistochemistry (IHC) on tissue microarrays (TMA). Further in vivo experiments corroborated the role of F3-T3 in enhancing glioma growth and progression.ConclusionF3-T3 facilitates the proliferation, invasion, migration and EMT of glioma cells, thereby promoting their malignant progression through STAT3 signaling activation. These findings highlight its potential as a therapeutic target for glioma treatment. |
| format | Article |
| id | doaj-art-b2bfe6e1c6cf4686a4035b36e1d87a22 |
| institution | OA Journals |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-b2bfe6e1c6cf4686a4035b36e1d87a222025-08-20T02:37:24ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-04-011510.3389/fonc.2025.15600081560008FGFR3-TACC3 fusion gene promotes glioblastoma malignant progression through the activation of STAT3 signaling pathwayYiming Li0Yiming Li1Jianshen Liang2Jianshen Liang3Jianshen Liang4Xiude Ren5Xiude Ren6Jiahe Guo7Jiahe Guo8Jiahe Guo9Xisen Wang10Xisen Wang11Xisen Wang12Xuya Wang13Xuya Wang14Xuya Wang15Shengping Yu16Shengping Yu17Tao Li18Tao Li19Xuejun Yang20Xuejun Yang21Xuejun Yang22Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaLaboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, ChinaObjectiveThe Fibroblast growth factor receptors 3-transforming acidic coiled-coil-containing protein 3 (FGFR3-TACC3, F3-T3) oncogenic fusion gene, identified in malignant tumors such as gliomas and bladder cancer, has been particularly noted in recurrent gliomas where it is considered to drive malignant progression, thus presenting itself as a viable therapeutic target. However, the precise mechanism by which F3-T3 facilitates the malignant progression of glioma is not fully understood.MethodsCorrection analysis of STAT3 and FGFR3 with major glioma mutation types and pan-cancer analysis was conducted using The Cancer Genome Atlas (TCGA) database. A series of phenotypic experiments, including CCK-8, EdU, colony-formation assay, wound healing assay, and transwell assay were conducted to detect the effects of F3-T3 on proliferation, invasion, and migration of glioma cells. The association between F3-T3 and epithelial-mesenchymal transition (EMT) was investigated through enrichment analysis of the E-MTAB-6037 gene chip database and confirmed by western blot. The underling mechanism were further inferred and validated through RNA sequencing, E-MTAB-6037 gene chip data, and western blot. The relationship between p-STAT3 expression and the WHO grade of glioma was evaluated using immunohistochemistry (IHC) and tissue microarray analysis. Furthermore, the results of vivo experiments and IHC has confirmed the impact of F3-T3 on glioma malignant progression and activation of the STAT3 signaling pathway.ResultsThe experimental results from this study indicate that F3-T3 accelerates the epithelial-mesenchymal transition (EMT) process in glioma cells, thereby promoting their proliferation, invasion, and migration capabilities. Mechanistically, it was determined through RNA sequencing that the signal transducer and activator of transcription 3 (STAT3) signaling pathway is crucial for the malignant progression of F3-T3. This finding was further supported through follow-up experiments conducted after STAT3 knockdown. The role of the STAT3 pathway in gliomas was also reinforced through bioinformatic analysis and immunohistochemistry (IHC) on tissue microarrays (TMA). Further in vivo experiments corroborated the role of F3-T3 in enhancing glioma growth and progression.ConclusionF3-T3 facilitates the proliferation, invasion, migration and EMT of glioma cells, thereby promoting their malignant progression through STAT3 signaling activation. These findings highlight its potential as a therapeutic target for glioma treatment.https://www.frontiersin.org/articles/10.3389/fonc.2025.1560008/fullFGFR3-TACC3 fusion genegliomamalignant progressioninvasionmigrationSTAT3 signaling pathway |
| spellingShingle | Yiming Li Yiming Li Jianshen Liang Jianshen Liang Jianshen Liang Xiude Ren Xiude Ren Jiahe Guo Jiahe Guo Jiahe Guo Xisen Wang Xisen Wang Xisen Wang Xuya Wang Xuya Wang Xuya Wang Shengping Yu Shengping Yu Tao Li Tao Li Xuejun Yang Xuejun Yang Xuejun Yang FGFR3-TACC3 fusion gene promotes glioblastoma malignant progression through the activation of STAT3 signaling pathway Frontiers in Oncology FGFR3-TACC3 fusion gene glioma malignant progression invasion migration STAT3 signaling pathway |
| title | FGFR3-TACC3 fusion gene promotes glioblastoma malignant progression through the activation of STAT3 signaling pathway |
| title_full | FGFR3-TACC3 fusion gene promotes glioblastoma malignant progression through the activation of STAT3 signaling pathway |
| title_fullStr | FGFR3-TACC3 fusion gene promotes glioblastoma malignant progression through the activation of STAT3 signaling pathway |
| title_full_unstemmed | FGFR3-TACC3 fusion gene promotes glioblastoma malignant progression through the activation of STAT3 signaling pathway |
| title_short | FGFR3-TACC3 fusion gene promotes glioblastoma malignant progression through the activation of STAT3 signaling pathway |
| title_sort | fgfr3 tacc3 fusion gene promotes glioblastoma malignant progression through the activation of stat3 signaling pathway |
| topic | FGFR3-TACC3 fusion gene glioma malignant progression invasion migration STAT3 signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1560008/full |
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