{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:02:17Z","timestamp":1790398937276,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Council for Scientific and Technological Development (CNPq)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Brazilian Federal Agency for Support and Evaluation of Higher Education (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brazil (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 inflammation-driven 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 wild-type Trp53\u00a0(+\/+), heterozygous (+\/\u2212), and knockout (\u2212\/\u2212) mice. Trp53\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms252010953","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T08:10:16Z","timestamp":1728634216000},"page":"10953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Trp53 Deletion Promotes Exacerbated Colitis, Facilitates Lgr5+ Cancer Stem Cell Expansion, and Fuels Tumorigenesis in AOM\/DSS-Induced Colorectal Cancer"],"prefix":"10.3390","volume":"25","author":[{"given":"Anderson F.","family":"Cunha","sequence":"first","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-90, RJ, Brazil"},{"name":"Instituto D\u2019Or de Ensino e Pesquisa, Rio de Janeiro 22281-100, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1141-5351","authenticated-orcid":false,"given":"Jo\u00e3o M.","family":"Delou","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-90, RJ, Brazil"},{"name":"Instituto D\u2019Or de Ensino e Pesquisa, Rio de Janeiro 22281-100, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro S.","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-90, RJ, Brazil"},{"name":"Departamento de Cl\u00ednica M\u00e9dica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8967-4486","authenticated-orcid":false,"given":"Julia S. M.","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-90, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen C. S.","family":"Souza","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednica M\u00e9dica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Chagas","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana C.","family":"Soletti","sequence":"additional","affiliation":[{"name":"Departamento Interdisciplinar, Universidade Federal do Rio Grande do Sul, Tramanda\u00ed 95590-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3647-7324","authenticated-orcid":false,"given":"Heitor S. P.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednica M\u00e9dica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2866-4223","authenticated-orcid":false,"given":"Helena L.","family":"Borges","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-90, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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