{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:33:26Z","timestamp":1777397606788,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"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 Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Cancer\u2010associated fibroblasts (CAFs) play a central role in cancer progression and are involved in modulating cancer cell proliferation, invasion, metastasis, drug resistance and so on. Receptor Interacting Serine\/Threonine Kinase 4 (RIPK4) was demonstrated to promote gastric cancer (GC) metastasis and tumorigenesis. Here, this study aimed to explore whether GC\u2010derived CAFs affected cisplatin (DDP) resistance in GC cells via RIPK4. DDP\u2010resistant GC cells were first established. Levels of RIPK4 mRNA and proteins were detected using qRT\u2010PCR and western blotting. The IC50 values of DDP, cell proliferation, invasion, and migration were analyzed using MTT, 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine, transwell, and wound healing assays, respectively. PI3K\/AKT pathway\u2010related proteins were measured by western blotting. Animal experiments were performed for in vivo analysis. Here, we found that CAFs enhanced DDP resistance in DDP\u2010resistant cells by promoting cell proliferation, invasion and migration. CAFs led to an increased RIPK4 expression in DDP\u2010resistant cells. The silencing of RIPK4 suppressed DDP resistance in DDP\u2010resistant cells. Moreover, RIPK4 silencing in CAFs could also reduce DDP resistance in GC. Mechanistically, CAFs could activate the PI3K\/AKT pathway by RIPK4. In vivo assay also showed that RIPK4 silencing in CAFs attenuated CAF\u2010induced DDP resistance. In conclusion, RIPK4\u2010decreased CAFs suppressed DDP resistance in GC by blocking the activation of the PI3K\/AKT pathway, recommending a novel method for overcoming DDP resistance in gastric cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70320","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T10:02:22Z","timestamp":1750068142000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cancer\u2010Associated Fibroblast\u2010Derived RIPK4 Confers Cisplatin Resistance in Gastric Cancer by Activating the PI3K\/AKT Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Rui","family":"Chen","sequence":"first","affiliation":[{"name":"Clinical Laboratory Central Hospital of Huanggang Huanggang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junfang","family":"Dai","sequence":"additional","affiliation":[{"name":"Infections Disease 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