{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:59:39Z","timestamp":1790416779958,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007179","name":"Advanced Centre for Treatment, Research and Education in Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007179","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/RLF\/Re\u2010entry\/19\/2020"],"award-info":[{"award-number":["BT\/RLF\/Re\u2010entry\/19\/2020"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/13\/IYBA\/2020\/14"],"award-info":[{"award-number":["BT\/13\/IYBA\/2020\/14"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    Cancer cachexia involves systemic metabolic deregulation along with classical features of muscle wasting, lipolysis, and chronic inflammation. While tumor nonautonomous effects on peripheral organs are recognized, how the tumor rewires the circulating immune cells and hematopoiesis remains unclear. We utilized a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    larval cancer cachexia model by expressing\n                    <jats:italic>yki<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>3SA<\/jats:italic>\n                    <\/jats:sup>\n                    in the adult midgut precursors (AMP), which gives rise to a tumor in the larval midgut and recapitulates key cachectic phenotypes, including insulin resistance. Tumor\u2010induced cachexia results in perturbed blood cell homeostasis with a reduced niche and aberrant blood cell differentiation in the larval hematopoietic organ, the lymph gland (LG). Circulating hemocytes in the tumor background display altered features with increased filopodia, phagocytic ability, and inflammatory gene signatures. Bulk RNA\u2010seq analysis of circulating hemocytes from tumor\u2010bearing larvae revealed upregulation of multiple cachectic ligands, notably ImpL2, an insulin antagonist. We demonstrate that elevated ImpL2 levels reduce LG niche size and promote widespread blood cell differentiation. Elevated ImpL2 levels and systemic insulin resistance in the tumor\u2010induced cachexia scenario both result in abrogation of insulin signaling in the niche\u2010progenitor micro\u2010environment in\u00a0the LG affecting Wingless signaling. Depletion of tumor\u2010derived ImpL2 is capable of rescuing cachectic phenotypes whereas depletion of hemocyte\u2010derived ImpL2 in the tumor background provides a partial rescue of cachectic phenotypes. Additionally, hemocyte ablation in the tumor background does not affect the tumor load but ameliorates the cachectic phenotypes. Our findings reveal that the tumor remodels hematopoiesis and blood cells which contribute to tissue wasting in cancer\u2010induced cachexia.\n                  <\/jats:p>","DOI":"10.1111\/febs.70741","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:36:51Z","timestamp":1790415411000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Drosophila<\/i>\n                    midgut tumor\u2010induced insulin resistance systemically remodels lymph gland hematopoiesis during cancer cachexia"],"prefix":"10.1111","author":[{"given":"Ujjayita","family":"Chowdhury","sequence":"first","affiliation":[{"name":"Stem Cell and Tissue Homeostasis Lab, Cancer Research Institute ACTREC \u2013 Tata Memorial Centre  Navi Mumbai India"},{"name":"Homi Bhabha National Institute  Mumbai 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\u2013 Tata Memorial Centre  Navi Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7297-2736","authenticated-orcid":false,"given":"Rohan Jayant","family":"Khadilkar","sequence":"additional","affiliation":[{"name":"Stem Cell and Tissue Homeostasis Lab, Cancer Research Institute ACTREC \u2013 Tata Memorial Centre  Navi Mumbai India"},{"name":"Homi Bhabha National Institute  Mumbai 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