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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Eukaryotic initiation factor 4E-binding protein 1 (EIF4EBP1\/4E-BP1) is a pivotal translational regulator with context-dependent roles in breast cancer pathogenesis. Its phosphorylation status, dynamically controlled by mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK)\/extracellular signal-regulated kinase (ERK), and AMP-activated protein kinase (AMPK) signaling, dictates a dualistic function: hypophosphorylated EIF4EBP1 suppresses oncogenesis by sequestering eIF4E and inhibiting cap-dependent translation of pro-tumorigenic mRNAs (e.g., cyclin D1 and c-MYC), while hyperphosphorylation promotes tumor progression and therapeutic resistance. EIF4EBP1 amplification (8p11-p12) is correlated with endocrine resistance and poor prognosis. EIF4EBP1 modulates cell cycle checkpoints, metabolic adaptation under stress, and resistance to cyclin-dependent kinase (CDK) 4 and 6 inhibitors and rapalogs via feedback loops (e.g., SGK3\/Akt reactivation). Emerging therapeutic strategies, such as ATP-competitive mTOR inhibitors, bisteric compounds, and agents targeting polyamine metabolism or upstream kinases, exploit the dynamics of EIF4EBP1 phosphorylation. As a biomarker, phosphorylated EIF4EBP1 levels predict tumor aggressiveness and treatment failure, positioning it as a critical node for precision oncology. Future research must address spatial heterogeneity and leverage multi-omics\/AI-driven approaches.<\/jats:p>","DOI":"10.31083\/fbl45484","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:35:31Z","timestamp":1788438931000},"source":"Crossref","is-referenced-by-count":0,"title":["EIF4EBP1 in Breast Cancer: Translational Control, Regulatory Networks, and Therapeutic Frontiers"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1176-1012","authenticated-orcid":true,"given":"Weijia","family":"Liu","sequence":"first","affiliation":[{"name":"College of Life Science, North China University of Science and Technology, 063210 Tangshan, Hebei, China"},{"name":"Jiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology, Suzhou Vocational Health College, 215009 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Hou","sequence":"additional","affiliation":[{"name":"Thyroid and Breast Surgery, Wuzhong People\u2019s Hospital of Suzhou City, 215128 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Life Science, Biology and Materials Engineering, Suzhou University of Science and Technology, 215009 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyu","family":"Mou","sequence":"additional","affiliation":[{"name":"Jiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology, Suzhou Vocational Health College, 215009 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Science, North China University of Science and Technology, 063210 Tangshan, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3920-1032","authenticated-orcid":true,"given":"Song-Bai","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science, North China University of Science and Technology, 063210 Tangshan, Hebei, China"},{"name":"Jiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology, Suzhou Vocational Health College, 215009 Suzhou, Jiangsu, China"},{"name":"School of Chemistry and Life Science, Biology and Materials Engineering, Suzhou University of Science and Technology, 215009 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology, Suzhou Vocational Health College, 215009 Suzhou, Jiangsu, China"},{"name":"Thyroid and Breast Surgery, Wuzhong People\u2019s Hospital of Suzhou City, 215128 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref1","unstructured":"Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, et al. 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