{"version":"6.9","hitCount":1,"resultList":{"result":[{"id":"PPR588446","source":"PPR","fullTextIdList":{"fullTextId":["PPR588446"]},"doi":"10.1101/2022.12.22.521159","title":"Mutation-induced phenotypic plasticity drives formation of a pro-metastatic tumour-intrinsic niche","authorString":"Bugter JM, El Bouazzaoui L, Küçükköse E, Mills ML, Hong Y, Sprangers J, Jordens I, Kokkinidi D, Plugge S, Venhuizen A, Bosman S, Hageman J, Fenderico N, Gilroy K, Montiel Gonzalez D, van Boxtel R, Suijkerbuijk SJ, Tejpar S, Campbell AD, Sansom OJ, Snippert HJ, Kranenburg O, Maurice MM.","authorList":{"author":[{"fullName":"Bugter JM","firstName":"Jeroen","lastName":"Bugter","initials":"JM","authorId":{"type":"ORCID","value":"0000-0001-9920-2937"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"El Bouazzaoui L","firstName":"Layla","lastName":"El Bouazzaoui","initials":"L","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"},{"affiliation":"Department of Surgical Oncology, Lab Translational Oncology, UMC Utrecht, the Netherlands"}]}},{"fullName":"Küçükköse E","firstName":"Emre","lastName":"Küçükköse","initials":"E","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Department of Surgical Oncology, Lab Translational Oncology, UMC Utrecht, the Netherlands"}]}},{"fullName":"Mills ML","firstName":"Megan","lastName":"Mills","initials":"ML","authorId":{"type":"ORCID","value":"0000-0001-6683-433X"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Department of Oncology, Katholieke Universiteit Leuven, Belgium"}]}},{"fullName":"Hong Y","firstName":"Yourae","lastName":"Hong","initials":"Y","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Sprangers J","firstName":"Joep","lastName":"Sprangers","initials":"J","authorId":{"type":"ORCID","value":"0000-0001-7865-2816"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Jordens I","firstName":"Ingrid","lastName":"Jordens","initials":"I","authorId":{"type":"ORCID","value":"0000-0003-3599-7931"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Kokkinidi D","firstName":"Danai","lastName":"Kokkinidi","initials":"D","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Princes Maxima Centre for Pediatric Oncology, Utrecht, the Netherlands"}]}},{"fullName":"Plugge S","firstName":"Susanna","lastName":"Plugge","initials":"S","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Princes Maxima Centre for Pediatric Oncology, Utrecht, the Netherlands"}]}},{"fullName":"Venhuizen A","firstName":"Anton","lastName":"Venhuizen","initials":"A","authorId":{"type":"ORCID","value":"0000-0002-3197-1307"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Division of Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, The Netherlands"}]}},{"fullName":"Bosman S","firstName":"Sabine","lastName":"Bosman","initials":"S","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Department of Oncology, Katholieke Universiteit Leuven, Belgium"}]}},{"fullName":"Hageman J","firstName":"Joris","lastName":"Hageman","initials":"J","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Fenderico N","firstName":"Nicola","lastName":"Fenderico","initials":"N","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Division of Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, The Netherlands"}]}},{"fullName":"Gilroy K","firstName":"Kathryn","lastName":"Gilroy","initials":"K","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Montiel Gonzalez D","firstName":"Diego","lastName":"Montiel Gonzalez","initials":"D"},{"fullName":"van Boxtel R","firstName":"Ruben","lastName":"van Boxtel","initials":"R"},{"fullName":"Suijkerbuijk SJ","firstName":"Saskia J.E.","lastName":"Suijkerbuijk","initials":"SJ"},{"fullName":"Tejpar S","firstName":"Sabine","lastName":"Tejpar","initials":"S"},{"fullName":"Campbell AD","firstName":"Andrew","lastName":"Campbell","initials":"AD"},{"fullName":"Sansom OJ","firstName":"Owen","lastName":"Sansom","initials":"OJ"},{"fullName":"Snippert HJ","firstName":"Hugo J.G.","lastName":"Snippert","initials":"HJ"},{"fullName":"Kranenburg O","firstName":"Onno","lastName":"Kranenburg","initials":"O"},{"fullName":"Maurice MM","firstName":"Madelon","lastName":"Maurice","initials":"MM"}]},"authorIdList":{"authorId":[{"type":"ORCID","value":"0000-0001-6683-433X"},{"type":"ORCID","value":"0000-0001-7865-2816"},{"type":"ORCID","value":"0000-0001-9920-2937"},{"type":"ORCID","value":"0000-0002-3197-1307"},{"type":"ORCID","value":"0000-0002-8983-9464"},{"type":"ORCID","value":"0000-0003-3599-7931"}]},"dataLinksTagsList":{"dataLinkstag":["altmetrics","supporting_data"]},"pubYear":"2022","abstractText":"Colorectal cancer (CRC) progression is characterised by a remarkable increase in plasticity and cellular heterogeneity  1,2 . The ability of cells to shift states and adopt mixed lineage potential exacerbates during metastasis and associates with poor patient survival  3 . How these atypical differentiated states emerge and drive cancer progression however has remained unclear. Here, we investigate this issue for BRAF-mutant CRC that commonly arise via the serrated pathway  4 and are linked to poor prognosis via incompletely understood progression steps. Using patient-derived organoids, gene editing and murine tumour models, we show that mutations in RNF43, a regulator of WNT receptor abundance  5 , endow BRAF-mutant CRC with metastatic capacity by driving a non-dividing tumour-intrinsic niche cell (TINC) state that provides growth factor self-sufficiency to the cancer tissue. TINCs are enriched in  RNF43 -mutant, mucinous and metastatic samples of human CRC, and ablation of TINCs lead to re-acquired external growth factor dependency during CRC organoid outgrowth. Together, our findings uncover a mechanism by which tumours leverage cellular plasticity to mediate self-organised stem– and niche-cell interactions. Our results argue that formation of a tumour-intrinsic niche is a prerequisite for BRAF-mutant CRC seeding to distant organs and that interference with niche formation may help avoid metastatic relapse.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"bioRxiv","yearOfPublication":2022},"grantsList":{"grant":[{"grantId":"91218050","agency":"ZonMw","orderIn":0}]},"fullTextUrlList":{"fullTextUrl":[{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Unpaywall","url":"https://www.biorxiv.org/content/biorxiv/early/2023/04/15/2022.12.22.521159.full.pdf"},{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.1101/2022.12.22.521159"},{"availability":"Open access","availabilityCode":"OA","documentStyle":"html","site":"Europe_PMC","url":"https://europepmc.org/article/PPR/PPR588446"},{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Europe_PMC","url":"https://europepmc.org/api/fulltextRepo?pprId=PPR588446&type=FILE&fileName=EMS158981-pdf.pdf&mimeType=application/pdf"}]},"isOpenAccess":"Y","inEPMC":"Y","inPMC":"N","hasPDF":"Y","hasBook":"N","hasSuppl":"Y","citedByCount":0,"hasData":"Y","hasReferences":"Y","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"Y","license":"cc by-nc-nd","hasEvaluations":"N","authMan":"N","epmcAuthMan":"Y","nihAuthMan":"N","manuscriptId":"EMS158981","hasTMAccessionNumbers":"Y","tmAccessionTypeList":{"accessionType":["doi"]},"dateOfCreation":"2022-12-24","firstIndexDate":"2022-12-24","fullTextReceivedDate":"2023-04-18","firstPublicationDate":"2022-12-23"}]}}