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However, the key metabolic factors that determine the risk of bone metastasis remain unclear. Here, we show that glucose transporter type 3 (SLC2A3) is notably overexpressed by lung cancer bone metastatic cells and tissues, as a facilitator of lung cancer bone metastasis. Additionally, SLC2A3 promotes glucose metabolism, which promotes tumor cell proliferation and metastasis via lactate\u2010mediated p53 lactylation. Within the tumor microenvironment, cancer cells serve as the primary source of secreted lactate, which induces protumor bone metastasis via osteoclast differentiation and suppresses the antitumor activity of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Subsequently, we developed Paris saponin VII, a SLC2A3 inhibitor that effectively suppressed bone metastasis in lung cancer bone metastasis mouse models and patient organoids. Notably, either inhibition of SLC2A3 or lactate limitation improved the tumor response and increased the sensitivity of lung cancer bone metastases to PD\u20101 treatment. Collectively, our findings highlight that targeting SLC2A3\u2010mediated lactate metabolism, either alone or in combination with PD\u20101 inhibition, is a potential strategy for treating lung cancer bone metastasis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202516622","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T19:23:20Z","timestamp":1770233000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["SLC2A3\u2010Mediated Lactate Metabolism Promotes Lung Cancer Bone Metastasis by Modulating P53 Lactylation and Immune Evasion"],"prefix":"10.1002","volume":"13","author":[{"given":"Yi","family":"Ding","sequence":"first","affiliation":[{"name":"Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University (Tongde Hospital of Zhejiang Province)  Hangzhou China"},{"name":"Jiangong Hospital Clinical Research Center East China Normal University  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