{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T03:27:06Z","timestamp":1761535626139,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Changzhou \u201cThe 14th Five-Year Plan\u201d High-Level Heath Talents Training Project","award":["2022CZZY005"],"award-info":[{"award-number":["2022CZZY005"]}]},{"name":"the Top Talent of Changzhou \u201cThe 14th Five-Year Plan\u201d High-Level Heath Talents Training Project","award":["2024CZBJ018"],"award-info":[{"award-number":["2024CZBJ018"]}]},{"name":"the Basic Research Project of Changzhou Medical Center of Nanjing Medical University","award":["CZKYCMC2024PY24"],"award-info":[{"award-number":["CZKYCMC2024PY24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Breast cancer (BRCA) remains a global health burden, with endocrine-resistant ER-positive BRCA posing therapeutic challenges. This study investigates STAMBP\u2019s role in breast cancer progression and evaluates its potential as a therapeutic target. Through siRNA library screening in ER-positive cell lines, we identified STAMBP as a key regulator of ER\u03b1 signaling and observed its upregulation in BRCA samples. (fold changes &gt; 2, sample sizes = 30, p &lt; 0.001), particularly in ER-positive subtypes. Prognostic analysis demonstrated that STAMBP overexpression correlates with poor clinical outcomes in ER-positive BRCA patients (p &lt; 0.05). In vitro functional assays showed STAMBP promoted proliferation, metastasis, and epithelial\u2013mesenchymal transition of ER-positive cells by regulating the activity of ER\u03b1 signaling. Mechanistically, the deubiquitinase STAMBP directly reduces the K48-linked polyubiquitination levels of ER\u03b1, enhancing its protein stability and activating downstream oncogenic signaling. STAMBP knockdown restored tamoxifen sensitivity in endocrine-resistant BRCA cells by reducing ER\u03b1 stability. This study has certain limitations, including the absence of pharmacological validation and reliance on small, single-center clinical cohorts, which should be addressed in future research to further substantiate the clinical relevance of targeting STAMBP in BRCA. Collectively, our findings identified STAMBP as a prognostic marker and demonstrated its dual role in driving ER-positive BRCA malignancy and mediating endocrine resistance. Targeting STAMBP may represent an innovative approach to improve endocrine therapeutic efficacy in ER-positive BRCA.<\/jats:p>","DOI":"10.3390\/biom15111502","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T02:50:48Z","timestamp":1761533448000},"page":"1502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["STAMBP Accelerates Progression and Tamoxifen Resistance of Breast Cancer Through Deubiquitinating ER\u03b1"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhihuai","family":"Wang","sequence":"first","affiliation":[{"name":"Department of General Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang 550001, China"},{"name":"Clinical Medical College, Guizhou Medical University, Guiyang 550001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Likai","family":"Gu","sequence":"additional","affiliation":[{"name":"Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xihu","family":"Qin","sequence":"additional","affiliation":[{"name":"Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7842-5283","authenticated-orcid":false,"given":"Chen","family":"Xiong","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Shandong University, Jinan 250012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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