{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:22:21Z","timestamp":1762179741090,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T00:00:00Z","timestamp":1762041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: The E26 transformation-specific (ETS) transcription factor Friend Leukemia Integration 1 (FLI1) has been linked to breast cancer aggressiveness, stromal remodeling, and immune modulation, yet the regulatory mechanisms governing its activity remain poorly defined. Of note, various studies have shown that EWS-FLI1-mediated transcription programs are facilitated via direct recruitment and binding of the NuRD-LSD1 complex, regulating its associated gene targets. Furthermore, LSD1 inhibition exhibited reverse transcriptional profiles driven by ETS-FLI and reduced in vivo tumorigenesis in cancers. Methods: We evaluated FLI1 expression across multiple invasive breast carcinoma (IBC) cohorts to determine its prognostic significance and associations with stromal features. In parallel, we investigated FLI1 regulation in humanized breast cancer mouse models treated with an LSD1 inhibitor. Results: High FLI1 expression was associated with advanced histological grade in IBC, consistent with an oncogenic function. FLI1-high tumors also exhibited elevated stromal and immune scores, indicating a role in remodeling the tumor microenvironment. Additionally, LSD1 inhibition downregulated FLI1 target genes involving angiogenesis and invasion. Conclusions: These findings highlight the dual role of FLI1: tumor-intrinsic FLI1 promotes proliferation and invasion, whereas its transcriptional regulation in tumor and endothelial compartments likely reflects LSD1 dependence. Collectively, our results support a mechanistic model in which LSD1\u2013FLI1 crosstalk is involved in immune and stromal remodeling, positioning FLI1 as both a marker of tumor aggressiveness and a potential predictor of response to epigenetic therapies in breast cancer.<\/jats:p>","DOI":"10.3390\/genes16111313","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:22:36Z","timestamp":1762176156000},"page":"1313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FLI1 Expression in Invasive Breast Carcinoma: Clinicopathological Correlations and Prognostic Implications"],"prefix":"10.3390","volume":"16","author":[{"given":"Nusrat Jahan","family":"Doly","sequence":"first","affiliation":[{"name":"Department of Pathology, Dhaka Medical College, Dhaka 1000, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Yeul","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pathology, Singapore General Hospital Academia, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazi Nafisa","family":"Tahsin","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Institute of Burn and Plastic Surgery, Dhaka 1000, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhuma","family":"Akhter","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dhaka Medical College, Dhaka 1000, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahana","family":"Sultana","sequence":"additional","affiliation":[{"name":"Department of Pathology, Greenlife Medical College, Dhaka 1205, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julekha","family":"Khatun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dhaka Medical College, Dhaka 1000, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue-zann","family":"Chua","sequence":"additional","affiliation":[{"name":"Division of Pathology, Singapore General Hospital Academia, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Tasleema","family":"Banu","sequence":"additional","affiliation":[{"name":"Translational Research and Innovation Laboratory, Singapore General Hospital Academia, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-1271","authenticated-orcid":false,"given":"Qingfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-1791","authenticated-orcid":false,"given":"Jabed","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Division of Pathology, Singapore General Hospital Academia, Singapore 169856, Singapore"},{"name":"Translational Research and Innovation Laboratory, Singapore General Hospital Academia, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.3892\/ijo.2020.5135","article-title":"Triple-negative breast cancer therapy: Current and future perspectives (Review)","volume":"57","author":"Won","year":"2020","journal-title":"Int. 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