{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:41Z","timestamp":1783574141826,"version":"3.55.0"},"reference-count":146,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Breast cancer continues to present formidable clinical challenges, particularly in triple-negative and endocrine-resistant subtypes where adaptive stress mechanisms drive therapeutic failure. Nuclear protein 1 (NUPR1), an intrinsically disordered protein, has emerged as a non-mutational hub that has been implicated in integrating metabolic, transcriptional, and cell-survival signals associated with malignant progression. This Review examines how NUPR1 transduces mitogenic stimuli into anabolic programs, while orchestrating autophagic flux, lysosomal biogenesis, and ferroptosis evasion to maintain cellular fitness under oncogenic and therapeutic stress. We discuss its causal roles in endocrine and chemoresistance through chromatin-associated cooperation with estrogen receptor \u03b1, activation of DNA-damage repair, and cell-cycle checkpoint control, as well as its contributions to metastatic dissemination via extracellular vesicle-mediated niche remodeling and immunosuppressive macrophage polarization. Furthermore, we evaluate emerging therapeutic avenues, from small-molecule inhibitors and single-domain antibody degraders that disrupt NUPR1 nuclear trafficking, to metabolic drug repurposing strategies such as statins that intercept the insulin\u2013NUPR1 axis. Elucidating NUPR1 biology represents a paradigm shift toward targeting dynamic, stress-adaptive dependencies in breast cancer, offering new precision-oncology opportunities.<\/jats:p>","DOI":"10.3389\/fphys.2026.1880388","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:21:04Z","timestamp":1783570864000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["NUPR1 in breast cancer: mechanisms and potential applications"],"prefix":"10.3389","volume":"17","author":[{"given":"Bo","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, Jilin Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Jilin Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Jilin Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Jilin Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078101","article-title":"Deciphering the binding between Nupr1 and MSL1 and their DNA-repairing activity","volume":"8","author":"Aguado-Llera","year":"2013","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cancergen.2022.11.001","article-title":"Multi-omics inference of differential breast cancer-related transcriptional regulatory network gene hubs between young Black and White patients","author":"Aguilar","year":"2023","journal-title":"Cancer Genet."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/cai2.70040","article-title":"Statins in breast cancer therapy: Mechanistic insights and emerging evidence","volume":"5","author":"Alim","year":"2026","journal-title":"Cancer Innov."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.149435","article-title":"Evaluating the therapeutic role of salvianolic acid A on pancreatic cancer cells through interaction with the intrinsically disordered protein NUPR1","volume":"337","author":"\u00c1lvarez-Rodr\u00edguez","year":"2026","journal-title":"Int. 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