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However, the origin of scirrhous CAFs remains unclear, and we here aimed to explore the epigenetic basis for scirrhous CAFs and their origin. Conditioned medium (CM) from scirrhous CAFs was shown to have a marked effect (2\u20134 folds) on the migration of gastric cancer cells compared to that from non\u2010scirrhous CAFs. The aggressive phenotype of scirrhous CAFs was associated with activation of TGF\u03b21 and NF\u2010\u03baB, along with increased expression of their downstream genes. Scirrhous CAFs had heavily acetylated super\u2010enhancers, and therapeutic targeting of super\u2010enhancers by a BET bromodomain inhibitor, mivebresib and JQ\u20101, markedly decreased their migration\u2010promoting activity. Notably, in scirrhous gastric cancer patients, normal fibroblasts in non\u2010cancerous tissues also had a strong migration\u2010promoting effect. It was suggested that fibroblasts in the non\u2010cancerous tissue of scirrhous gastric patients have already acquired tumor\u2010promoting capacity, forming a stromal field for scirrhous gastric cancer although its spatial extent remains to be solved.<\/jats:p>","DOI":"10.1111\/cas.70408","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:16:42Z","timestamp":1777861002000},"page":"1894-1906","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Super\u2010Enhancer Formation in Scirrhous Gastric\n                    <scp>CAFs<\/scp>\n                    , and the Presence of a Stromal Field in Non\u2010Cancerous Tissues"],"prefix":"10.1111","volume":"117","author":[{"given":"Yoshimi","family":"Yasukawa","sequence":"first","affiliation":[{"name":"Department of Epigenomics, Institute for Advanced Life Sciences Hoshi University  Tokyo 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