{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:47:31Z","timestamp":1782110851139,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lactic acid in the tumor microenvironment (TME) drives triple\u2010negative breast cancer (TNBC) progression by coordinately reprogramming lipid metabolism and suppressing immune function. RNA\u2010Seq analysis of lactate\u2010treated MDA\u2010MB\u2010231 and NK\u201092 cells revealed simultaneous activation of the TGF\u2010\u03b2\/Smad pathway and upregulation of lipid metabolism genes (FASN, ACSL1). Functionally, lactate treatment increased TGF\u2010\u03b2 protein levels by approximately 3.5\u2010fold, significantly enhancing TNBC cell invasion (~3\u2010fold) and colony formation (~2.4\u2010fold), while concurrently impairing NK cell cytotoxicity through upregulated PD\u20101 expression (~3\u2010fold) and suppressed IFN\u2010\u03b3 secretion (&gt;60% reduction). These pro\u2010metastatic and immunosuppressive effects were effectively reversed by TGF\u2010\u03b2 receptor inhibition (SB\u2010431542) or Smad2 knockdown. In mouse xenograft models, lactic acid accelerated tumor growth and increased lung metastatic nodules by ~4\u2010fold, whereas blocking TGF\u2010\u03b2 signaling reduced tumor burden by approximately 60% and restored NK cell activity. Our findings establish lactic acid as a metabolic\u2010immune regulator that synergistically fuels TNBC metastasis through TGF\u2010\u03b2\/Smad\u2010mediated lipid reprogramming and immune suppression, offering novel therapeutic targets.<\/jats:p>","DOI":"10.1002\/jbt.70938","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T12:58:39Z","timestamp":1781269119000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactic Acid Promotes TNBC Lung Metastasis via TGF\u2010\u03b2\/Smad\u2010Driven Lipid Metabolic Toxicity and NK Cell Dysfunction"],"prefix":"10.1002","volume":"40","author":[{"given":"Peiling","family":"Zhu","sequence":"first","affiliation":[{"name":"The Fifth Department of General Surgery The Second Hospital of Hebei Medical University Shijiazhuang 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