2. Academic Validation
  3. Fn14 Controls the SIRT2-Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer

Fn14 Controls the SIRT2-Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer

  • Adv Sci (Weinh). 2025 Jul;12(27):e2501552. doi: 10.1002/advs.202501552.
Anyue Wu 1 2,  Shengze Li 3,  Chunyang Feng 1 2,  Ruiju He 1 2,  Ruolan Wu 1 2,  Zhijun Hu 1 2,  Jinhua Huang 1 2,  Wenjing Wang 2,  Lei Huang 3,  Lihua Qiu 1 2 4
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, 200127, China.
  • 2 Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, China.
  • 3 Department 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, China.
  • 4 State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
PMID: 40344622 DOI: 10.1002/advs.202501552
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.

Keywords

Fn14; deacetylation of slug; epithelial‐mesenchymal transition; metastasis of epithelial ovarian cancer; post‐translational modifications.

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