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Hybrid epithelial\u2010mesenchymal transition (EMT) cells within the tumors are correlated with augmented proliferative capacity and facilitation of lung metastasis. Single\u2010cell RNA sequencing and spatial transcriptomic sequencing are employed to reveal the hybrid EMT subsets within the vascular fibroblast microenvironment. These hybrid EMT cells exhibit a pro\u2010tumorigenic impact in vitro. Notably, cadherin 11 (CDH11), a specific marker for hybrid EMT cells, may exert its regulatory role in cellular function by interfering with branched\u2010chain amino acids\u00a0(BCAA) metabolism by inhibiting branched\u2010chain ketoacid dehydrogenase to activate the mammalian target of the rapamycin pathway, thus making it a potential therapeutic target for SACC. Furthermore, celecoxib and its derivatives are specific CDH11 inhibitors that regulate BCAA metabolism, increase reactive oxygen species production, and subsequently activate the cyclic GMP\u2010AMP synthase\u2010stimulator of the interferongene\u00a0pathway (cGAS\u2010STING). They also inhibit lung metastasis in NOD\u2010SCID mice in vivo. Overall, these findings suggest a promising treatment strategy that targets hybrid EMT cells to mitigate lung metastasis in SACC. Celecoxib may serve as a promising clinical intervention for the treatment of lung metastases in patients with SACC.<\/jats:p>","DOI":"10.1002\/advs.202408751","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:39:36Z","timestamp":1735630776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of CDH11 Activates cGAS\u2010STING by Stimulating Branched Chain Amino Acid Catabolism and Mitigates Lung Metastasis of Adenoid Cystic Carcinoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Rui\u2010Feng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Peking University School and Hospital of Stomatology  Beijing 100081 P. R. China"},{"name":"Central Laboratory Peking University School and Hospital of Stomatology  Beijing 100081 P. R. China"},{"name":"National Center for Stomatology  Beijing 100081 P. R. 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