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This study investigated how lactylation of TRIM29 contributes to the invasive behavior of GC and lymph node metastasis and the efficacy of chemotherapy for the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined the expression levels of TRIM29 and its lactylation status in GC tissues and cell lines using quantitative reverse-transcription polymerase chain reaction, immunohistochemistry based on tissue microarrays and western blotting. Functional transwell migration, three-dimensional invasion assay and tube formation assays were performed to assess the role of TRIM29 in GC. The interaction between TRIM29 and heteronuclear ribonucleoprotein A1(hnRNPA1) was explored by co-immunoprecipitation and mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Expression of TRIM29 was significantly upregulated in GC tissues in comparison with adjacent non-tumor tissues. This upregulation was associated with lymph node metastasis, vascular tumors and a worse prognosis. Lactylation of TRIM29 in GC cells enhanced the migratory ability and invasiveness of these cells and lymph node metastasis. Mechanistically, TRIM29 formed a complex with hnRNPA1, which in turn activated the Wnt\/\u03b2-catenin signaling pathway by stabilizing \u03b2-catenin in a ubiquitination-dependent manner. Targeting TRIM29 and lymphangiogenesis augmented the efficacy of 5-fluorouracil-based chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lactylation of TRIM29 promotes invasive behavior and lymph node metastasis in GC cells by engaging the hnRNPA1-mediated Wnt\/\u03b2-catenin pathway. Targeting TRIM29 and lymphangiogenesis may be a promising therapeutic strategy for patients with advanced GC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41419-026-08468-9","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T18:35:54Z","timestamp":1771007754000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lactylation-drived TRIM29 induces invasive behavior and lymph node metastasis in gastric cancer via hnRNPA1-mediated Wnt\/\u03b2-catenin pathway"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4418-7895","authenticated-orcid":false,"given":"Ruheng","family":"Hua","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7459-1045","authenticated-orcid":false,"given":"Yuanjie","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5829-0289","authenticated-orcid":false,"given":"Zhenwei","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7907-2475","authenticated-orcid":false,"given":"Boyang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3413-624X","authenticated-orcid":false,"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7858-1173","authenticated-orcid":false,"given":"Jianwei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1507-8069","authenticated-orcid":false,"given":"Qingfeng","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"8468_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104470","volume":"202","author":"Y Wang","year":"2024","unstructured":"Wang Y, Ding G, Chu C, Cheng XD, Qin JJ. 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