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This study tested whether deleting Trp53 alters inflammation-driven tumor growth and Lgr5+ cancer stem cell expression in mice. Using AOM/DSS-induced colon tumorigenesis in wild-type, heterozygous, and knockout strains, Trp53−/− mice showed heightened DSS colitis sensitivity and rapid, aggressive tumor formation. Knockouts selectively increased Lgr5+ colon cancer stem-like cells, boosted laminin, and shortened AOM/DSS latency, improving tumor induction efficiency.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/trp53-deletion-promotes-exacerbated-colitis-facilitates-lgr5-cancer-stem-cell-expansion-fuels-tumorigenesis-in-aomdss-induced-colorectal-cancer/331458/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/trp53-deletion-promotes-exacerbated-colitis-facilitates-lgr5-cancer-stem-cell-expansion-fuels-tumorigenesis-in-aomdss-induced-colorectal-cancer/331458.png","ImageObject",300,407,{"name":92,"@type":93},"Sage","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What hypothesis does the study test about Trp53 deletion?","Question",{"text":112,"@type":113},"The study investigates whether deleting Trp53 affects inflammation-induced tumor growth and the expression of Lgr5+ cancer stem cells in mice.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What mouse model and experimental groups were used?",{"text":117,"@type":113},"Researchers used AOM/DSS-induced colon tumorigenesis in wild-type Trp53 (+/+), heterozygous (+/−), and knockout (−/−) mice.",{"name":119,"@type":110,"acceptedAnswer":120},"How does Trp53 loss impact disease severity and tumor development?",{"text":121,"@type":113},"Trp53−/− mice showed increased sensitivity to DSS colitis and earlier accelerated tumorigenesis with 100% incidence, with knockout tumors exhibiting the most aggressive features.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331458,1790183350,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},687197207057,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Article  \nTrp53 Deletion Promotes Exacerbated Colitis, Facilitates Lgr5+ Cancer Stem Cell Expansion, and Fuels Tumorigenesis in AOM/DSS-Induced Colorectal Cancer  \nAnderson F. Cunha 1,2,†, João M. Delou 1,2,†, Pedro S. Barbosa 1,3, Julia S. M. Conceição 1, Karen C. S. Souza 3, Vera Chagas 4, Rossana C. Soletti 5, Heitor S. P. de Souza 3 and Helena L. Borges 1, *  \nCitation: Cunha, A.F.; Delou, J.M.; Barbosa, P.S.; Conceição, J.S.M.; Souza, K.C.S.; Chagas, V.; Soletti, R.C.; de Souza, H.S.P.; Borges, H.L. Trp53 Deletion Promotes Exacerbated Colitis, Facilitates Lgr5+ Cancer Stem Cell Expansion, and Fuels Tumorigenesis in AOM/DSS-Induced Colorectal Cancer. Int. J. Mol. Sci. 2024, 25, 10953. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms252010953](10.3390/ijms252010953)  \nAcademic Editor: Donatella Delle Cave  \nReceived: 20 September 2024  \nAccepted: 7 October 2024  \nPublished: 11 October 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-90, RJ, Brazil;  \n[7andersonfaletti7@gmail.com](7andersonfaletti7@gmail.com) (A.F.C.); [joao.delou@idor.org](joao.delou@idor.org) (J.M.D.); [phsalesbarbosa@gmail.com](phsalesbarbosa@gmail.com) (P.S.B.);  \n[juliasoutomc@gmail.com](juliasoutomc@gmail.com) (J.S.M.C.)  \n2 Instituto D’Or de Ensino e Pesquisa, Rio de Janeiro 22281-100, RJ, Brazil  \n3 Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro,  \nRio de Janeiro 21941-913, RJ, Brazil; [karenecris480@ufrj.br](karenecris480@ufrj.br) (K.C.S.S.); [heitor.souza@gmail.com](heitor.souza@gmail.com) (H.S.P.d.S.)  \n4 Departamento de Patologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; [veraachagas@gmail.com](veraachagas@gmail.com)  \n5 Departamento Interdisciplinar, Universidade Federal do Rio Grande do Sul, Tramandaí 95590-000, RS, Brazil; [rossana.soletti@ufrgs.br](rossana.soletti@ufrgs.br)  \n* [Correspondence: hborges@icb.ufrj.br](Correspondence: hborges@icb.ufrj.br)[ ](Correspondence: hborges@icb.ufrj.br)† These authors contributed equally to this work.  \nAbstract: Colorectal cancer CRC remains one of the leading causes of cancer-related deaths worldwide, with chronic intestinal inflammation identified as a major risk factor. Notably, the tumor suppressor TP53 undergoes mutation at higher rates and earlier stages during human inflammationdriven colon tumorigenesis than in sporadic cases. We investigated whether deleting Trp53 affects inflammation-induced tumor growth and the expression of Lgr5+ cancer stem cells in mice. We examined azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis in wildtype Trp53 (+/+), heterozygous (+/−), and knockout (−/−) mice. Trp53−/− mice showed increased sensitivity to DSS colitis and earlier accelerated tumorigenesis with 100% incidence. All groups could develop invasive tumors, but knockouts displayed the most aggressive features. Unlike wild-type CRC, knockouts selectively showed increased populations of Lgr5+ colon cancer stem-like cells. Trp53 loss also boosted laminin, possibly facilitating the disruption of the tumor border. This study highlights how Trp53 deletion promotes the perfect storm of inflammation and stemness, driving colon cancer progression. Trp53 deletion dramatically shortened AOM/DSS latency and improved tumor induction efficiency, offering an excellent inflammation-driven CRC model.  \nKeywords: colorectal cancer; p53; Lgr5; inflammatory bowel disease  \n1. Introduction  \nColorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of canc","cbCaiawUWayEu12s","https://ap.wps.com/l/cbCaiawUWayEu12s","pdf",1847447,18,"English","# Abstract\n# Introduction\n## CRC and inflammation as risk factors\n## TP53/Trp53 in CRC progression\n## p53 regulation and tumor microenvironment\n## Lgr5+ intestinal stem cells and cancer stem cells\n## Rationale: p53 and differentiation in stem cells","[{\"question\":\"What hypothesis does the study test about Trp53 deletion?\",\"answer\":\"The study investigates whether deleting Trp53 affects inflammation-induced tumor growth and the expression of Lgr5+ cancer stem cells in mice.\"},{\"question\":\"What mouse model and experimental groups were used?\",\"answer\":\"Researchers used AOM/DSS-induced colon tumorigenesis in wild-type Trp53 (+/+), heterozygous (+/−), and knockout (−/−) mice.\"},{\"question\":\"How does Trp53 loss impact disease severity and tumor development?\",\"answer\":\"Trp53−/− mice showed increased sensitivity to DSS colitis and earlier accelerated tumorigenesis with 100% incidence, with knockout tumors exhibiting the most aggressive features.\"}]","Trp53 Deletion Promotes Exacerbated Colitis - Facilitates Lgr5+ Cancer Stem Cell Expansion - Fuels Tumorigenesis in AOM/DSS-Induced Colorectal Cancer | PDF",1789993318,45]