{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:32:18Z","timestamp":1783539138609,"version":"3.55.0"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"28","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370395"],"award-info":[{"award-number":["82370395"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070079"],"award-info":[{"award-number":["82070079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wuhan Municipal health Commission","award":["WX23Q09"],"award-info":[{"award-number":["WX23Q09"]}]},{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["2023AFB355"],"award-info":[{"award-number":["2023AFB355"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wuhan Science and Technology Bureau","award":["2024020801020395"],"award-info":[{"award-number":["2024020801020395"]}]},{"name":"Key Project of the Joint Fund for Translational Medicine and Interdisciplinary Research, Zhongnan Hospital of Wuhan University","award":["ZNJC202515"],"award-info":[{"award-number":["ZNJC202515"]}]},{"name":"Key Project of the Joint Fund for Translational Medicine and Interdisciplinary Research, Zhongnan Hospital of Wuhan University","award":["ZNJC202515"],"award-info":[{"award-number":["ZNJC202515"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:p>\n                    Metastasis in gastric cancer requires metabolic reprogramming, but its key drivers remain unclear. Using a CRISPR-Cas9 metabolic knockout screen integrated with patient transcriptomes, we identified the mitochondrial enzyme ALDH6A1 as an anti-invasive factor.\n                    <jats:italic toggle=\"yes\">ALDH6A1<\/jats:italic>\n                    down-regulation blocked the terminal step of valine catabolism and caused intracellular accumulation of methylmalonic acid (MMA). MMA competitively occupied the \u03b1-ketoglutarate (\u03b1-KG) cofactor pocket of the histone demethylase KDM5C, suppressing its activity and increasing H3K4 dimethylation (H3K4me2) at promoters of invasion-related genes, including\n                    <jats:italic toggle=\"yes\">ANGPT2<\/jats:italic>\n                    (angiopoietin-2) and\n                    <jats:italic toggle=\"yes\">MMP7<\/jats:italic>\n                    (matrix metalloproteinase 7). This epigenetic reprogramming promoted gastric cancer liver metastasis in mice. Pharmacologic ALDH6A1 activation with Alda-1 or systemic MMA clearance with\n                    <jats:sc>l<\/jats:sc>\n                    -carnitine lowered H3K4me2, dampened the invasive program, and reduced metastatic burden. These findings identify the ALDH6A1-MMA axis as a targetable metabolic-epigenetic pathway in gastric cancer metastasis.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb2892","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T18:00:55Z","timestamp":1783533655000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Reprogramming of valine metabolism mediated by abnormally low ALDH6A1 expression promotes invasive metastasis of gastric cancer"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6353-3525","authenticated-orcid":true,"given":"Jipeng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China."},{"name":"Hubei Key Laboratory of Tumor Biological Behaviours, Wuhan 430071, China."},{"name":"Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1752-8384","authenticated-orcid":true,"given":"Lei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China."},{"name":"Hubei Key Laboratory of Tumor Biological Behaviours, Wuhan 430071, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2093-0796","authenticated-orcid":true,"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hantao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, 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China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Nie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China."},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China."},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal 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