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Adv."],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:p>\n                    Lactate in the tumor microenvironment (TME) is typically generated by cells exhibiting high glycolytic flux, exemplified by tumor cells. However, in glycolysis-low malignancies such as prostate cancer, stroma-derived lactate may drive noncanonical signaling and functions that remain unclear. Here, we identified APCDD1\n                    <jats:sup>+<\/jats:sup>\n                    cancer-associated fibroblasts (CAFs) as a distinct stromal population that secretes lactate into the TME in response to androgen deprivation therapy (ADT). Lactate uptake by prostate cancer cells induces androgen receptor variant 7 expression, thereby conferring resistance to ADT. Mechanistically, lactate-induced lactylation of the spliceosome component SNRPA at Lys\n                    <jats:sup>123<\/jats:sup>\n                    (K123) enhances its recognition of cis-acting elements, increases chromatin binding, and promotes androgen receptor splicing. Targeting lactate transport with monocarboxylate transporter inhibitors effectively restores ADT sensitivity. These findings reveal a metabolic-epigenetic axis linking lactate in the microenvironment to alternative splicing regulation and suggest a promising therapeutic strategy to overcome ADT resistance.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ady5324","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:59:06Z","timestamp":1768589946000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Lactate derived from cancer-associated fibroblasts promotes alternative splicing and castration resistance in prostate cancer"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0955-9591","authenticated-orcid":true,"given":"Diwei","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Urology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. 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