ArticleCell death and differentiation2014
Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating Kras(G12D)-induced senescence.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- NUPR1 as a central stress-adaptation node in cancer: integrating metabolic rewiring, cell death, and therapy resistance.Journal of biomedical science · 2026Review
- Article
- Downregulation of Sod2 increases atypical flat lesions and dysplasia to advance pancreatic ductal adenocarcinoma.Molecular cancer · 2025Article
- Senescence program and its reprogramming in pancreatic premalignancy.Cell death & disease · 2023Review
- Review
- Review
- Review
- Histone methyltransferase Dot1L inhibits pancreatic cancer cell apoptosis by promoting NUPR1 expression.The Journal of international medical research · 2022Article
- The Role of Nonapoptotic Programmed Cell Death - Ferroptosis, Necroptosis, and Pyroptosis - in Pancreatic Ductal Adenocarcinoma Treatment.Frontiers in oncology · 2022Review
- Radiation-Induced Senescence in p16+/LUC Mouse Lung Compared to Bone Marrow Multilineage Hematopoietic Progenitor Cells.Radiation research · 2021Article
- Article
- CircRNA HIPK3 promotes the progression of oral squamous cell carcinoma through upregulation of the NUPR1/PI3K/AKT pathway by sponging miR-637.Annals of translational medicine · 2021Article
- Human Endogenous Retrovirus (HERV)-KInternational journal of molecular sciences · 2021Article
- Intrinsically Disordered Proteins as Regulators of Transient Biological Processes and as Untapped Drug Targets.Molecules (Basel, Switzerland) · 2021Review
- The Paradoxical Role of Cellular Senescence in Cancer.Frontiers in cell and developmental biology · 2021Review
- Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice.Scientific reports · 2020Article
- Targeting intrinsically disordered proteins involved in cancer.Cellular and molecular life sciences : CMLS · 2020Review
- The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage.Nature communications · 2020Article
- Review
- NUPR1 acts as a pro-survival factor in human bone marrow-derived mesenchymal stem cells and is induced by the hypoxia mimetic reagent deferoxamine.Journal of clinical biochemistry and nutrition · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Nuclear protein 1 (Nupr1), a small chromatin protein, has a critical role in cancer development, progression and resistance to therapy. Previously, we had demonstrated that Nupr1 cooperates with Kras(G12D) to induce pancreas intraepithelial neoplasias (PanIN) formation and pancreatic ductal adenocarcinoma development in mice. However, the molecular mechanisms by which Nupr1 influences Kras-mediated preneoplastic growth remain to be fully characterized. In the current study, we report evidence supporting a role for Nupr1 as a gene modifier of Kras(G12D)-induced senescence, which must be overcome to promote PanIN formation. We found that genetic inactivation of Nupr1 in mice impairs Kras-induced PanIN, leading to an increase in β-galactosidase-positive cells and an upregulation of surrogate marker genes for senescence. More importantly, both of these cellular and molecular changes are recapitulated by the results of mechanistic experiments using RNAi-based inactivation of Nupr1 in human pancreatic cancer cell models. In addition, the senescent phenotype, which results from Nupr1 inactivation, is accompanied by activation of the FoxO3a-Skp2-p27(Kip1)-pRb-E2F pathway in vivo and in vitro. Thus, combined, these results show, for the first time, that Nupr1 aids oncogenic Kras to bypass senescence in a manner that cooperatively promotes PanIN formation. Besides its mechanistic importance, this new knowledge bears medical relevance as it delineates early pathobiological events that may be targeted in the future as a means to interfere with the formation of preneoplastic lesions early during pancreatic carcinogenesis.
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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.