ArticleCell cycle (Georgetown, Tex.)2011
p53-dependent regulation of growth, epithelial-mesenchymal transition and stemness in normal pancreatic epithelial cells.
Article in Cell cycle (Georgetown, Tex.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- SPRED2 suppresses the stemness of hepatocellular carcinoma through the p53/miR-506-3p/KLF4 pathway.Cancer biology & medicine · 2026Article
- Article
- Age-Related Decline in Pancreas Regeneration Is Associated With an Increased Proinflammatory Response to Injury.Gastro hep advances · 2024Article
- Review
- Pancreatic acinar cell fate relies on system xCell death & disease · 2023Article
- New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.Seminars in cancer biology · 2023Review
- Polo-like kinase 4 (Plk4) potentiates anoikis-resistance of p53KO mammary epithelial cells by inducing a hybrid EMT phenotype.Cell death & disease · 2023Article
- Article
- Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus onInternational journal of molecular sciences · 2021Review
- Mutations of p53 associated with pancreatic cancer and therapeutic implications.Annals of hepato-biliary-pancreatic surgery · 2021Review
- CENP-A overexpression promotes distinct fates in human cells, depending on p53 status.Communications biology · 2021Article
- Review
- Deficient or R273H and R248W Mutations of p53 Promote Chemoresistance to 5-FUFrontiers in cell and developmental biology · 2021Article
- Article
- Cancer Stemness: p53 at the Wheel.Frontiers in oncology · 2020Review
- Krüppel‑like factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway.Molecular medicine reports · 2019Article
- p53 balances between tissue hierarchy and anarchy.Journal of molecular cell biology · 2019Review
- Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer.Journal of cancer metastasis and treatment · 2019Article
- SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer.Journal of oncology · 2019Review
- ROBO2 is a stroma suppressor gene in the pancreas and acts via TGF-β signalling.Nature communications · 2018Article
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic acinar cells acquire in vitro a pancreatic progenitor phenotype associated with activation of p53, growth arrest and senescence. A similar program is also activated in chronic pancreatitis. To assess the mechanisms involved in this process, we cultured pancreatic acinar cells from wild-type, p53(-/-), p16(-/-) and p21(-/-) mice. Cultures from p53(-/-) mice, but not those from p16(-/-) or p21(-/-) mice, display an enhanced proliferation and can be expanded continuously for more than 20 passages. p53(-/-) cells also display features of stemness such as enhanced sphere formation, increased expression of pancreatic multipotent progenitor markers (Ptf1a, Pdx1, Cpa1, c-myc, Sox9 and Hnf1b), and of the stemness regulators Bmi1 and Klf4. Upon subculture, p53(-/-) cells undergo an epithelial-mesenchymal transition (EMT) and express high levels of vimentin and of the transcriptional regulators Snai1, Snai2, Twist, Zeb1 and Zeb2. Genetic lineage tracing unequivocally demonstrates the epithelial origin of the cells with mesenchymal phenotype. These cells express the endodermal markers Hhex, Pdx1, Sox9, Hnf1b, Foxa2, Gata6 and Sox17, and the stem cell markers c-myc, Bmi1 and Klf4. Cultures from p53(+/-) mice display intermediate levels of the transcription factors involved in EMT but do not surpass the growth arrest. Our findings support the notion that p53 controls both growth and epithelial cell differentiation in the pancreas. These observations have important implications regarding the mechanisms through which p53 inactivation in tumors may be associated with aggressive biological behavior.
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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.