ArticleCancer research2015
Targeted Deletion of p53 in Lgr5-Expressing Intestinal Stem Cells Promotes Colon Tumorigenesis in a Preclinical Model of Colitis-Associated Cancer.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Liquid biopsy biomarkers for early detection of gastrointestinal cancers: Current landscape and emerging technologies.Clinical and translational medicine · 2026Review
- p53 terminates the regenerative fetal-like state after colitis-associated injury.Science advances · 2024Article
- Trp53 Deletion Promotes Exacerbated Colitis, Facilitates Lgr5+ Cancer Stem Cell Expansion, and Fuels Tumorigenesis in AOM/DSS-Induced Colorectal Cancer.International journal of molecular sciences · 2024Article
- Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets.Signal transduction and targeted therapy · 2024Review
- Amaryllidaceae Alkaloids Decrease the Proliferation, Invasion, and Secretion of Clinically Relevant Cytokines by Cultured Human Colon Cancer Cells.Biomolecules · 2022Article
- Identification of hub genes and pathways in colitis-associated colon cancer by integrated bioinformatic analysis.BMC genomic data · 2022Article
- Dietary Flavonoids in p53-Mediated Immune Dysfunctions Linking to Cancer Prevention.Biomedicines · 2020Review
- Environmental exposures, stem cells, and cancer.Pharmacology & therapeutics · 2019Review
- Mutations in foregut SOX2Protein & cell · 2019Article
- Two decades of embryonic stem cells: a historical overview.Human reproduction open · 2019Article
- Role of p53 in the Regulation of the Inflammatory Tumor Microenvironment and Tumor Suppression.Cancers · 2018Review
- Article
- A matter of life and death: stem cell survival in tissue regeneration and tumour formation.Nature reviews. Cancer · 2018Review
- Shaping functional gut microbiota using dietary bioactives to reduce colon cancer risk.Seminars in cancer biology · 2017Review
- Rapidly cycling Lgr5Cell death & disease · 2016Article
- Current understanding concerning intestinal stem cells.World journal of gastroenterology · 2016Review
- Immunohistochemical Expression of CD133 and LGR5 in Ulcerative Colitis-associated Colorectal Cancer and Dysplasia.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
p53 has been shown to mediate cancer stem-like cell function by suppressing pluripotency and cellular dedifferentiation. However, there have been no studies to date that have addressed the specific effects of p53 loss in colonic adult stem cells. In this study, we investigated the consequences of conditionally ablating p53 in the highly relevant Lgr5(+) stem cell population on tumor initiation and progression in the colon. In a mouse model of carcinogen (AOM)-induced colon cancer, tamoxifen-inducible Lgr5-driven deletion of p53 reduced apoptosis and increased proliferation of crypt stem cells, but had no effect on tumor incidence or size. Conversely, in a mouse model of colitis-associated cancer, in which mice are exposed to AOM and the potent inflammation inducer DSS, stem cell-specific p53 deletion greatly enhanced tumor size and incidence in the colon. These novel findings suggest that the loss of p53 function in stem cells enables colonic tumor formation only when combined with DNA damage and chronic inflammation. Furthermore, we propose that stem cell targeting approaches are valuable for interrogating prevention and therapeutic strategies that aim to specifically eradicate genetically compromised stem cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.