{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:00:39Z","timestamp":1790413239788,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["256f0137009j0001"],"award-info":[{"award-number":["256f0137009j0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ama121018"],"award-info":[{"award-number":["JP24ama121018"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cancer cachexia is a devastating systemic syndrome, yet tumor\u2010intrinsic programs that enable cachexia induction remain poorly defined. Here we dissect cachexia\u2010inducing tumor evolution using a uniquely paired model derived from a rare human duodenal neuroendocrine carcinoma, in which repeated in vivo passaging converts a non\u2010cachexia\u2010inducing cell line (TCC\u2010NECT\u20102) into a cachexia\u2010inducing derivative (AkuNEC). AkuNEC xenografts reproducibly induced progressive body weight loss, whereas TCC\u2010NECT\u20102 xenografts did not. Using data\u2010independent acquisition (DIA) proteomics, we quantified the proteomes of the paired cell lines and their matched xenograft tumors and performed complementary comparisons (cell line\u2013to\u2013cell line, cell\u2013to\u2013tumor within each lineage, and tumor\u2013to\u2013tumor). Proteomic profiling revealed robust divergence between TCC\u2010NECT\u20102 and AkuNEC cells in vitro, and extensive remodeling upon xenograft formation in both lineages. Importantly, cachexia\u2010inducing tumors displayed lineage\u2010specific in vivo remodeling and an in vivo tumor proteome enriched for epithelial\u2013mesenchymal transition, hypoxia, and cholesterol homeostasis, whereas no significant pathway enrichment was detected among proteins decreased in AkuNEC tumors under the applied false discovery rate (FDR) threshold. These results establish cachexia as an acquired tumor phenotype shaped by in vivo selection and provide a proteome\u2010wide resource for prioritizing tumor\u2010intrinsic candidates for future functional studies.<\/jats:p>","DOI":"10.1002\/pmic.70153","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:50:21Z","timestamp":1781286621000},"page":"73-83","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteome\u2010Wide Dissection of Cachexia\u2010Inducing Evolution in a Paired Human Neuroendocrine Carcinoma Cell Line Model"],"prefix":"10.1002","volume":"26","author":[{"given":"Julia","family":"Osaki","sequence":"first","affiliation":[{"name":"Division of Rare Cancer Research National Cancer Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yomogi","family":"Shiota","sequence":"additional","affiliation":[{"name":"Division of Rare Cancer Research National Cancer Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Yanagihara","sequence":"additional","affiliation":[{"name":"Division of Rare Cancer Research National Cancer Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumio","family":"Ohtsuki","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Division of Rare Cancer Research National Cancer Center  Tokyo 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