{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:07:08Z","timestamp":1790802428238,"version":"4.1.0"},"posted":{"date-parts":[[2024,9,11]]},"group-title":"Cancer Biology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cell biology and genetic analysis of intracellular, intercellular and inter-organ interaction studies in animal models are key for understanding development, physiology, and disease. The MARCM technique can emulate tumor development by simultaneous clonal tumor suppressor loss-of-function generation coupled with GAL4-UAS-driven oncogene and marker expression, but the utility is limited for studying tumor-host interactions due to genetic constraints. To overcome this, we introduce EyaHOST, a novel system that replaces MARCM with the QF2-QUAS binary gene expression system under the\n                  <jats:italic>eya<\/jats:italic>\n                  promoter control, unleashing the fly community genome-wide GAL4-UAS driven tools to manipulate any host cells or tissue at scale. EyaHOST generates epithelial clones in the eye epithelium similar to MARCM. EyaHOST-driven Ras\n                  <jats:sup>V12<\/jats:sup>\n                  oncogene overexpression coupled with scribble tumor suppressor knockdown recapitulates key cancer features, including systemic catabolic switching and organ wasting. We demonstrate effective tissue-specific manipulation of host compartments such as neighbouring epithelial cells, immune cells, fat body, and muscle using fly avatars with tissue-specific GAL4 drivers. Organ-specific inhibition of autophagy or stimulation of growth-signaling through PTEN knockdown in fat body or muscle prevents cachexia-like wasting. Additionally, we show that\n                  <jats:italic>\n                    Ras\n                    <jats:sup>V12<\/jats:sup>\n                    , scrib\n                    <jats:sup>RNAi<\/jats:sup>\n                  <\/jats:italic>\n                  tumors induce caspase-driven apoptosis in the epithelial microenvironment. Inhibition of apoptosis by p35 expression in the microenvironment promotes tumor growth. EyaHOST offers a versatile modular platform for dissecting tumor-host interactions and other mechanisms involving intercellular and inter-organ communication in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  .\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:p>\n                    *\n                    <jats:italic>eyes absent<\/jats:italic>\n                    , eye disc-specific enhancer drives clonal KD recombinase flip-out activated QF2 expression in the larval eye epithelium for simultaneous QUAS-driven gain and loss-of-function analysis of gene function.\n                  <\/jats:p>\n                  <jats:p>*Clones are visualized by QUAS-tagBFP or QUAS-eGFP facilitating analysis of existing fluorescent reporters.<\/jats:p>\n                  <jats:p>*The GAL4-UAS system and existing genome-wide genetic tools are released to independently manipulate any cell population in the animal for cell biology, intercellular or inter-organ analysis for developmental, physiological, or disease model analysis.<\/jats:p>\n                  <jats:p>*Fly avatars for tumor-host interaction studies with multiple organs allow live monitoring and manipulation of tumors and organs in translucent larva.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.06.611647","type":"posted-content","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T11:31:29Z","timestamp":1726054289000},"source":"Crossref","is-referenced-by-count":2,"title":["EyaHOST, a modular genetic system for investigation of intercellular and tumor-host interactions\n                  <i>in Drosophila melanogaster<\/i>"],"prefix":"10.64898","author":[{"given":"Jos\u00e9","family":"Teles-Reis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6549-2788","authenticated-orcid":false,"given":"Ashish","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rojyar","family":"Khezri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Micheli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia Alfonso","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9150-2676","authenticated-orcid":false,"given":"Tor Erik","family":"Rusten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024091311401116000_2024.09.06.611647v1.1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.202390"},{"key":"2024091311401116000_2024.09.06.611647v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90033-0"},{"key":"2024091311401116000_2024.09.06.611647v1.3","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1998.0591"},{"key":"2024091311401116000_2024.09.06.611647v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1197142"},{"key":"2024091311401116000_2024.09.06.611647v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7169-5_13"},{"key":"2024091311401116000_2024.09.06.611647v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/131.3.643"},{"key":"2024091311401116000_2024.09.06.611647v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/144.4.1673"},{"key":"2024091311401116000_2024.09.06.611647v1.8","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.4.851"},{"key":"2024091311401116000_2024.09.06.611647v1.9","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/152.4.1631"},{"key":"2024091311401116000_2024.09.06.611647v1.10","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.2.401"},{"key":"2024091311401116000_2024.09.06.611647v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.320"},{"key":"2024091311401116000_2024.09.06.611647v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01791-4"},{"key":"2024091311401116000_2024.09.06.611647v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088474"},{"key":"2024091311401116000_2024.09.06.611647v1.14","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg548"},{"key":"2024091311401116000_2024.09.06.611647v1.15","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00051"},{"key":"2024091311401116000_2024.09.06.611647v1.16","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"2024091311401116000_2024.09.06.611647v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1525"},{"key":"2024091311401116000_2024.09.06.611647v1.18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168873"},{"key":"2024091311401116000_2024.09.06.611647v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21148"},{"key":"2024091311401116000_2024.09.06.611647v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00387-5"},{"key":"2024091311401116000_2024.09.06.611647v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80701-1"},{"key":"2024091311401116000_2024.09.06.611647v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.09.009"},{"key":"2024091311401116000_2024.09.06.611647v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.08.008"},{"key":"2024091311401116000_2024.09.06.611647v1.24","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107336"},{"key":"2024091311401116000_2024.09.06.611647v1.25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158317"},{"key":"2024091311401116000_2024.09.06.611647v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.03.001"},{"key":"2024091311401116000_2024.09.06.611647v1.27","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.039727"},{"key":"2024091311401116000_2024.09.06.611647v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/nature20815"},{"key":"2024091311401116000_2024.09.06.611647v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.137"},{"key":"2024091311401116000_2024.09.06.611647v1.30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03189"},{"key":"2024091311401116000_2024.09.06.611647v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/nature14298"},{"key":"2024091311401116000_2024.09.06.611647v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.392"},{"key":"2024091311401116000_2024.09.06.611647v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.11.036"},{"key":"2024091311401116000_2024.09.06.611647v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2011.09.005"},{"key":"2024091311401116000_2024.09.06.611647v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/nature08702"},{"key":"2024091311401116000_2024.09.06.611647v1.36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009376107"},{"key":"2024091311401116000_2024.09.06.611647v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.05.014"},{"key":"2024091311401116000_2024.09.06.611647v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601401"},{"key":"2024091311401116000_2024.09.06.611647v1.39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1701791114"},{"key":"2024091311401116000_2024.09.06.611647v1.40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5351"},{"key":"2024091311401116000_2024.09.06.611647v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.025"},{"key":"2024091311401116000_2024.09.06.611647v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2023.05.071"},{"key":"2024091311401116000_2024.09.06.611647v1.43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2020120118"},{"key":"2024091311401116000_2024.09.06.611647v1.44","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6371-3_3"},{"key":"2024091311401116000_2024.09.06.611647v1.45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111704108"},{"key":"2024091311401116000_2024.09.06.611647v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1561"},{"key":"2024091311401116000_2024.09.06.611647v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-05991-5"},{"key":"2024091311401116000_2024.09.06.611647v1.48","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.000950"},{"key":"2024091311401116000_2024.09.06.611647v1.49","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.94073"},{"key":"2024091311401116000_2024.09.06.611647v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.02.012"},{"key":"2024091311401116000_2024.09.06.611647v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.06.064"},{"key":"2024091311401116000_2024.09.06.611647v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.11.007"},{"key":"2024091311401116000_2024.09.06.611647v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.01.016"},{"key":"2024091311401116000_2024.09.06.611647v1.54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001140"},{"key":"2024091311401116000_2024.09.06.611647v1.55","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.21.012804.093845"},{"key":"2024091311401116000_2024.09.06.611647v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.50"},{"key":"2024091311401116000_2024.09.06.611647v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.47"},{"key":"2024091311401116000_2024.09.06.611647v1.58","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00247-07"},{"key":"2024091311401116000_2024.09.06.611647v1.59","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.110.119917"},{"key":"2024091311401116000_2024.09.06.611647v1.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.07.002"},{"key":"2024091311401116000_2024.09.06.611647v1.61","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2020.603397"},{"key":"2024091311401116000_2024.09.06.611647v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-07852-7"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.09.06.611647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:01:36Z","timestamp":1768460496000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.09.06.611647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,11]]},"references-count":62,"URL":"https:\/\/doi.org\/10.1101\/2024.09.06.611647","relation":{},"subject":[],"published":{"date-parts":[[2024,9,11]]},"subtype":"preprint"}}