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Multiple studies have found that its expression is abnormal in various tumors, influencing their occurrence, development, or prognosis. Our previous research indicated that down\u2010regulating ESRP2 can suppress the proliferation of breast cancer (BC) cells, specifically the MCF\u20107 line. To delve deeper into the role of ESRP2 in BC cells, we investigated its impact on the migration of BC cells in vitro and the underlying molecular mechanisms. The outcomes of the in vitro scratch assay and Transwell assay initially confirmed that ESRP2 hinders the migration of both MCF\u20107 and MDA\u2010MB\u2010231 cells, and that reducing ESRP2 expression enhances their migratory capacity. We demonstrated that the down\u2010regulation of ESRP2 can boost the migration ability of MCF\u20107 cells, and increase the mRNA expression of epithelial\u2010mesenchymal transition (EMT) transcription factor ZEB2 and related markers N\u2010cadherin and Vimentin. This suggests that ESRP2 plays a potential regulatory role in inhibiting EMT transcription program. Additionally, results from RNA sequencing and agarose electrophoresis gel experiments predict that down\u2010regulating ESRP2 may promote exon skipping of the ENAH gene by modulating the alternative splicing of genes associated with cell migration, driving the shift of MCF\u20107 cells from an epithelial to a mesenchymal phenotype. Our research reveals a novel mechanism by which ESRP2 affects BC metastasis through post\u2010transcriptional regulation. ESRP2 may present as a promising biomarker in combating BC cell migration by targeting EMT.<\/jats:p>","DOI":"10.1002\/mc.70093","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:16:29Z","timestamp":1770718589000},"page":"545-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of ESRP2 Promotes Breast Cancer Cell Migration by Activating EMT Transcription Program Through Modulation of ENAH Variable Splicing"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2211-7895","authenticated-orcid":false,"given":"Yuting","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy Guangzhou Red Cross Hospital of Jinan University, Guangzhou Guangdong China"},{"name":"School of Pharmaceutical Sciences Southern Medical University, Guangzhou Guangdong 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