Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer
Abstract Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of cancer research. Fibroblast growth factor‐inducible 14 (Fn14) has been shown to regulate wound...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-07-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202501552 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849719882363437056 |
|---|---|
| author | Anyue Wu Shengze Li Chunyang Feng Ruiju He Ruolan Wu Zhijun Hu Jinhua Huang Wenjing Wang Lei Huang Lihua Qiu |
| author_facet | Anyue Wu Shengze Li Chunyang Feng Ruiju He Ruolan Wu Zhijun Hu Jinhua Huang Wenjing Wang Lei Huang Lihua Qiu |
| author_sort | Anyue Wu |
| collection | DOAJ |
| description | Abstract Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of cancer research. Fibroblast growth factor‐inducible 14 (Fn14) has been shown to regulate wound repair, inflammation, angiogenesis, and chemoresistance, but its functional role in metastasis in EOC is still unknown. Here it is reported that Fn14 is identified as a cancer metastasis suppressor that inhibits the migratory and invasive potential of EOC cells by down‐regulating epithelial‐mesenchymal transition (EMT). Mechanistically, it is identified that Fn14 promotes acetylation‐dependent protein degradation of Slug, a key transcriptional factor associated with EMT. The deacetylase Sirtuin 2 (SIRT2) has been reported to be involved in the deacetylation of Slug protein to stabilize it and then prevent its degradation in the nucleus. The results showed that Fn14 alters the subcellular localization of (SIRT2) by interacting with SIRT2, leading to reduced SIRT2 shuttling into the nucleus and subsequently promoting the acetylated degradation of Slug. Collectively, the work has demonstrated for the first time that Fn14 inhibits EOC metastasis by regulating SIRT2‐mediated Slug deacetylation, providing a new perspective and method for the development of future novel therapeutic strategies for the treatment of EOC metastasis. |
| format | Article |
| id | doaj-art-3ecd3d4205d94951b8b19dac6e365bb2 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-3ecd3d4205d94951b8b19dac6e365bb22025-08-20T03:12:02ZengWileyAdvanced Science2198-38442025-07-011227n/an/a10.1002/advs.202501552Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian CancerAnyue Wu0Shengze Li1Chunyang Feng2Ruiju He3Ruolan Wu4Zhijun Hu5Jinhua Huang6Wenjing Wang7Lei Huang8Lihua Qiu9Department of Obstetrics and Gynecology Ren Ji Hospital School of Medicine Shanghai JiaoTong University Shanghai 200127 ChinaDepartment of Histoembryology Genetics and Developmental Biology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Key Laboratory of Reproductive Medicine Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Obstetrics and Gynecology Ren Ji Hospital School of Medicine Shanghai JiaoTong University Shanghai 200127 ChinaDepartment of Obstetrics and Gynecology Ren Ji Hospital School of Medicine Shanghai JiaoTong University Shanghai 200127 ChinaDepartment of Obstetrics and Gynecology Ren Ji Hospital School of Medicine Shanghai JiaoTong University Shanghai 200127 ChinaDepartment of Obstetrics and Gynecology Ren Ji Hospital School of Medicine Shanghai JiaoTong University Shanghai 200127 ChinaDepartment of Obstetrics and Gynecology Ren Ji Hospital School of Medicine Shanghai JiaoTong University Shanghai 200127 ChinaShanghai Key Laboratory of Gynecologic Oncology Shanghai 200127 ChinaDepartment of Histoembryology Genetics and Developmental Biology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Key Laboratory of Reproductive Medicine Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Obstetrics and Gynecology Ren Ji Hospital School of Medicine Shanghai JiaoTong University Shanghai 200127 ChinaAbstract Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of cancer research. Fibroblast growth factor‐inducible 14 (Fn14) has been shown to regulate wound repair, inflammation, angiogenesis, and chemoresistance, but its functional role in metastasis in EOC is still unknown. Here it is reported that Fn14 is identified as a cancer metastasis suppressor that inhibits the migratory and invasive potential of EOC cells by down‐regulating epithelial‐mesenchymal transition (EMT). Mechanistically, it is identified that Fn14 promotes acetylation‐dependent protein degradation of Slug, a key transcriptional factor associated with EMT. The deacetylase Sirtuin 2 (SIRT2) has been reported to be involved in the deacetylation of Slug protein to stabilize it and then prevent its degradation in the nucleus. The results showed that Fn14 alters the subcellular localization of (SIRT2) by interacting with SIRT2, leading to reduced SIRT2 shuttling into the nucleus and subsequently promoting the acetylated degradation of Slug. Collectively, the work has demonstrated for the first time that Fn14 inhibits EOC metastasis by regulating SIRT2‐mediated Slug deacetylation, providing a new perspective and method for the development of future novel therapeutic strategies for the treatment of EOC metastasis.https://doi.org/10.1002/advs.202501552deacetylation of slugepithelial‐mesenchymal transitionFn14metastasis of epithelial ovarian cancerpost‐translational modifications |
| spellingShingle | Anyue Wu Shengze Li Chunyang Feng Ruiju He Ruolan Wu Zhijun Hu Jinhua Huang Wenjing Wang Lei Huang Lihua Qiu Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer Advanced Science deacetylation of slug epithelial‐mesenchymal transition Fn14 metastasis of epithelial ovarian cancer post‐translational modifications |
| title | Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer |
| title_full | Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer |
| title_fullStr | Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer |
| title_full_unstemmed | Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer |
| title_short | Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer |
| title_sort | fn14 controls the sirt2 mediated deacetylation of slug to inhibit the metastasis of epithelial ovarian cancer |
| topic | deacetylation of slug epithelial‐mesenchymal transition Fn14 metastasis of epithelial ovarian cancer post‐translational modifications |
| url | https://doi.org/10.1002/advs.202501552 |
| work_keys_str_mv | AT anyuewu fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT shengzeli fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT chunyangfeng fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT ruijuhe fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT ruolanwu fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT zhijunhu fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT jinhuahuang fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT wenjingwang fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT leihuang fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer AT lihuaqiu fn14controlsthesirt2mediateddeacetylationofslugtoinhibitthemetastasisofepithelialovariancancer |