Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter
Abstract Background Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. Methods Employing sophisticated m...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05085-y |
| _version_ | 1797259092545241088 |
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| author | Songwei Feng Bo Ding Zhu Dai Han Yin Yue Ding Sicong Liu Ke Zhang Hao Lin Zhongdang Xiao Yang Shen |
| author_facet | Songwei Feng Bo Ding Zhu Dai Han Yin Yue Ding Sicong Liu Ke Zhang Hao Lin Zhongdang Xiao Yang Shen |
| author_sort | Songwei Feng |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. Methods Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression. Results Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth. Conclusion Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression. |
| first_indexed | 2024-04-24T23:03:56Z |
| format | Article |
| id | doaj.art-a5b8efa55c004261a814273d0e0d5737 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-24T23:03:56Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-a5b8efa55c004261a814273d0e0d57372024-03-17T12:36:47ZengBMCJournal of Translational Medicine1479-58762024-03-0122112510.1186/s12967-024-05085-yCancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoterSongwei Feng0Bo Ding1Zhu Dai2Han Yin3Yue Ding4Sicong Liu5Ke Zhang6Hao Lin7Zhongdang Xiao8Yang Shen9Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast UniversityState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast UniversityDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Clinical Science and Research, Zhongda Hospital, School of Medicine, Southeast UniversityState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast UniversityDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast UniversityAbstract Background Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. Methods Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression. Results Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth. Conclusion Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.https://doi.org/10.1186/s12967-024-05085-yOvarian cancerFGF7Epithelial-mesenchymal transitionCAFsFGFR2 |
| spellingShingle | Songwei Feng Bo Ding Zhu Dai Han Yin Yue Ding Sicong Liu Ke Zhang Hao Lin Zhongdang Xiao Yang Shen Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter Journal of Translational Medicine Ovarian cancer FGF7 Epithelial-mesenchymal transition CAFs FGFR2 |
| title | Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter |
| title_full | Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter |
| title_fullStr | Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter |
| title_full_unstemmed | Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter |
| title_short | Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter |
| title_sort | cancer associated fibroblast secreted fgf7 as an ovarian cancer progression promoter |
| topic | Ovarian cancer FGF7 Epithelial-mesenchymal transition CAFs FGFR2 |
| url | https://doi.org/10.1186/s12967-024-05085-y |
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