{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:54:09Z","timestamp":1790949249597,"version":"4.1.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":85,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Oncol."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Protein lactylation, a novel post-translational modification utilizing lactate as the substrate, has emerged as a key mechanism linking metabolic alterations to cancer progression. This study aims to investigate the role and underlying mechanism of S100A11 lactylation in gastric cancer progression and metastasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Lactylome profiling, site-directed mutagenesis, co-IP, cycloheximide chase, ubiquitination assays, and in vitro\/in vivo functional experiments were performed to dissect the regulatory effect of S100A11 lactylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>S100A11 was identified as a hyperlactylated protein in gastric cancer tissues, with lysine 27 (K27) and lysine 55 (K55) serving as the primary modification sites. Mechanistically, lactylation at K27 and K55 disrupted the interaction between S100A11 and its E3 ubiquitin ligase FBXW11, thereby inhibiting polyubiquitination and proteasomal degradation of the protein. The K27R\/K55R double mutation, which abolished both lactylation and ubiquitination at these residues, resulted in constitutive stabilization of S100A11. The stabilized S100A11 hyperactivated the PI3K-AKT and ERK1\/2 signaling cascades and upregulated the downstream oncogenic effectors Cyclin D1 and c-Myc. Functionally, S100A11 stabilization significantly enhanced the proliferation, colony formation, migration and invasion of gastric cancer cells in vitro, and markedly promoted lung metastasis in vivo. Clinically, higher lactylation levels of S100A11 were observed in patients with advanced TNM stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals a lactylation-ubiquitination competitive regulatory mechanism that governs S100A11 protein stability, which directly links Warburg effect-derived lactate to oncogenic protein stabilization and metastatic progression in gastric cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s13402-026-01255-w","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T07:36:17Z","timestamp":1783582577000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactylation shields S100A11 from degradation to promote gastric cancer metastasis"],"prefix":"10.1007","volume":"49","author":[{"given":"Qingrui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingrui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"issue":"1","key":"1255_CR1","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"R.L. 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The use of human tissue samples was approved by the Institutional Review Board (IRB approval number: 2023-KY-174). All patients provided written informed consent prior to sample collection. Animal experiments were approved by the Ethics Committee of China-Japan Friendship Hospital, China (approval number: ZRDWLL260017). All procedures involving animals followed institutional guidelines for the care and use of laboratory animals, and efforts were made to minimize suffering.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"130"}}