{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:34:18Z","timestamp":1787567658614,"version":"build-2736575974"},"reference-count":78,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573636"],"award-info":[{"award-number":["82573636"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82573636"],"award-info":[{"award-number":["82573636"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Jiangsu Province Capability Improvement Project through Science, Technology and Education","award":["ZDXK202222"],"award-info":[{"award-number":["ZDXK202222"]}]},{"name":"the Postgraduate Research & Practice Innovation Program of Jiangsu Province","award":["JX10214342"],"award-info":[{"award-number":["JX10214342"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Triple-negative breast cancer (TNBC) lacks effective targeted therapies, and its dependence on glycolysis represents a potential metabolic vulnerability. EIF3H, the largest subunit of the eukaryotic translation initiation factor 3 complex and a putative deubiquitinase, has been implicated in tumor progression, but its role in TNBC metabolism remains unclear. Methods: EIF3H expression and prognostic value were evaluated in public datasets, clinical TNBC specimens, and cell lines. Functional roles were examined using proliferation, colony formation, migration, and xenograft assays. Mechanisms were investigated by mass spectrometry, co-immunoprecipitation, ubiquitination and glycolytic rate assays, macrophage co-culture, and single-cell transcriptomic analysis. Results: EIF3H was significantly upregulated in TNBC and associated with poor survival. Transcriptionally activated by TRPS1, EIF3H bound to lactate dehydrogenase A (LDHA), reduced its ubiquitination, and prevented its proteasomal degradation. LDHA stabilization enhanced glycolysis and lactate production, thereby promoting TNBC cell proliferation and migration in vitro and tumor growth in vivo; these effects were abolished by LDHA knockdown and restored by LDHA re-expression. In addition, tumor-derived lactate induced M2 macrophage polarization via GPR65, which in turn reinforced malignant progression. Conclusions: Our findings define a TRPS1\u2013EIF3H\u2013LDHA axis that drives glycolysis-dependent TNBC progression and reveal lactate\u2013GPR65 signaling as a mediator of tumor\u2013macrophage crosstalk, supporting EIF3H as a potential prognostic biomarker and therapeutic target in TNBC.<\/jats:p>","DOI":"10.3390\/cancers18172735","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EIF3H Modulates Glycolysis Through LDHA Stabilization in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1454-0531","authenticated-orcid":false,"given":"Xuyu","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghai","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1172\/JCI45014","article-title":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","volume":"121","author":"Lehmann","year":"2011","journal-title":"J. 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