{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:18:43Z","timestamp":1790684323756,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colorectal cancer (CRC) represents a major cause of cancer\u2010related mortality worldwide. Exosomes derived from cancer\u2010associated fibroblasts (CAFs\u2010Exo) transfer oncogenic signals to cancer cells, promoting tumor growth, metastasis, and glutamine metabolism. However, the specific contribution of CAFs\u2010Exo to the pathogenesis of CRC is still largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The conditioned medium of CAFs (CAF\u2010CM) and CAFs\u2010Exo were used to treat CRC cells. The effects on cell behaviors were evaluated by measuring cell viability, proliferation, migration, invasion, and sphere formation. The influence on glutamine metabolism was assessed by detecting glutamine consumption and glutamine and \u03b1\u2010ketoglutarate production. MeRIP, RIP, RNA pull\u2010down, and mRNA stability assays were used to assess the METTL1\/SLC1A5 mRNA interaction. Animal experiments were used to evaluate the function of CAFs\u2010Exo in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CAF\u2010CM promoted CRC cell proliferation, migration, invasion, sphere formation, and glutamine metabolism in\u00a0vitro. CAF\u2010CM increased METTL1 expression and m7G modification levels in CRC cells. Si\u2010METTL1\u2013CAF\u2010CM exerted inhibitory effects on CRC cell malignant behaviors and glutamine metabolism. Mechanistically, METTL1 stabilized SLC1A5 mRNA by mediating its m7G modification. SLC1A5 overexpression reversed the inhibitory effects of si\u2010METTL1\u2013CAF\u2010CM on CRC cell malignant behaviors and glutamine metabolism. Furthermore, CAFs\u2010Exo increased METTL1 protein levels in CRC cells. Sh\u2010METTL1\u2013CAFs\u2010Exo suppressed tumor growth and lung metastasis in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings identify a novel CAFs\u2010Exo\/METTL1\/SLC1A5 axis that drives CRC progression partially by reprogramming glutamine metabolism, revealing new potential therapeutic targets for CRC treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.70334","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T03:24:42Z","timestamp":1773372282000},"page":"1541-1555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exosomes From Cancer\u2010Associated Fibroblasts Promote Colorectal Cancer Progression and Glutamine Metabolism Through METTL1\u2010Mediated m7G Modification of SLC1A5 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