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The objective of this study was to explore the function of FMNL3 in breast cancer progression and endeavor to reveal the molecular mechanism of this phenomenon. We found that FMNL3 was abnormally highly expressed in aggressive breast cancer cells and tissues, and it significantly inhibited E\u2010cadherin expression. FMNL3 could specifically interact with Twist1 rather than other epithelial\u2013mesenchymal transition transcription factors (EMT\u2010TFs). We also found that FMNL3 enhanced the repressive effect of Twist1 on <jats:italic>CDH1<\/jats:italic> transcription in breast cancer cells. Further mechanism studies showed that FMNL3 suppressed the ubiquitin degradation of Twist1 by inhibiting the interaction between Twist1 and Rad23B, the ubiquitin transfer protein of Twist1. In vitro functional experiments, it was confirmed that FMNL3 promoted the migration and invasion of breast cancer cells by regulating Twist1. Furthermore, Twist1 could directly bind to the <jats:italic>fmnl3<\/jats:italic> promoter to facilitate FMNL3 transcription. To conclude, this study indicated that FMNL3 acted as a pro\u2010metastasis factor in breast cancer by promoting Twist1 stability to suppress <jats:italic>CDH1<\/jats:italic> transcription.<\/jats:p>","DOI":"10.1002\/jcp.31481","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T09:49:14Z","timestamp":1732528154000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["FMNL3 Promotes Migration and Invasion of Breast Cancer Cells via Inhibiting Rad23B\u2010Induced Ubiquitination of Twist1"],"prefix":"10.1002","volume":"240","author":[{"given":"Binggong","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Bioengineering and Key Laboratory of Protein Modification and Disease Dalian University of Technology Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Man","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Cancer Hospital of Dalian University of Technology Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Key Laboratory of Protein Modification and Disease Dalian University of Technology Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Cancer Hospital of Dalian University of Technology Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Cancer Hospital of Dalian University of Technology Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Kang","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Key Laboratory of Protein Modification and Disease Dalian University of Technology Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Key Laboratory of Protein Modification and Disease Dalian University of Technology Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Cancer Hospital of Dalian University of Technology Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bashir","family":"Ahmad","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Key Laboratory of Protein Modification and Disease Dalian University of Technology Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Cancer Hospital of Dalian University of Technology Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Cancer Hospital of Dalian University of Technology Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5257-0089","authenticated-orcid":false,"given":"Huijian","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Key Laboratory of Protein Modification and Disease Dalian University of Technology Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Alboukadel K. 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