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Despite advances in risk stratification, biomarkers predicting metastatic potential remain limited. Here, we identify lactate as a critical driver of PTC metastasis through lactylation of carnitine palmitoyltransferase 1\u2009A (CPT1A), the rate-limiting enzyme in fatty acid \u03b2-oxidation (FAO). Multi-omics profiling of 27 paired PTC tissues revealed elevated lactate levels and FAO activation, corroborated by TCGA data. Functional assays demonstrated that exogenous lactate enhances PTC cell migration via CPT1A-dependent FAO. Mechanistically, lactate upregulated CPT1A transcription by promoting histone H3K18 lactylation (H3K18la), simultaneously stabilized CPT1A protein via lactylation of CPT1A at K180\/K285 to suppress its ubiquitin-proteasomal degradation. Genetic or pharmacological inhibition of CPT1A abolished lactate-driven migration and FAO activity. In vivo, lactylation-deficient CPT1A mutants (K180R\/K285R) attenuated lung metastasis and subcutaneous tumor growth in nude mice. This study reveals that lactate-CPT1A axis synergistically amplifies FAO to fuel PTC progression, suggesting CPT1A lactylation as a therapeutic vulnerability for metabolic intervention.<\/jats:p>","DOI":"10.1038\/s41419-026-08790-2","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T12:07:57Z","timestamp":1777291677000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lactic acid promotes metastasis of papillary thyroid carcinoma by enhancing CPT1A lactylation"],"prefix":"10.1038","volume":"17","author":[{"given":"Mingjian","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruowen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxu","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojia","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Materazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Miccoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5561-4964","authenticated-orcid":false,"given":"Xuetian","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"8790_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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