ArticleProceedings of the National Academy of Sciences of the United States of America2010
Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 410 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
410 citing papers in PubMed, 1 synthesis or guideline pooled it, 679 citations in OpenAlex.
- Pooled it
- Trial
- Diet-Induced Phospholipid Remodeling Dictates Ferroptosis Sensitivity and Tumorigenesis in the Pancreas.Cancer discovery · 2026Article
- Review
- Biological Resectability in Colorectal Liver Metastases: A Nomogram-Based Continuous Risk Model to Define Borderline Disease.Annals of gastroenterological surgery · 2026Article
- KRAS is required for plexiform neurofibroma formation and represents a targetable vulnerability in established tumors.Science advances · 2026Article
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Nature communications · 2026Article
- Antibody subclass deficiency accelerates tumorigenesis in genetically engineered mouse models of pancreatic cancer.JCI insight · 2026Article
- Increased mRNA translation delays tumour initiation and exposes a therapeutic vulnerability in lung cancer.Molecular cancer · 2026Article
- Spliceosome induction is a druggable dependency of RAS-driven senescence and cancer.Nature communications · 2026Article
- Cyclin C promotes pancreatic developmentand suppresses cancer initiation by maintenance of the autophagy-lysosome pathway.iScience · 2026Article
- Microenvironmental acidosis drives PARP- and ATM inhibitor resistance in p53 deficient pancreatic cancer.iScience · 2026Article
- The emerging role of exosomal circRNAs in modulating apoptotic pathways and overcoming cancer therapy resistance.Discover oncology · 2026Review
- Ubiquitination of Oncogenic Mutant p53 via Attenuation of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth.Molecular cancer therapeutics · 2026Article
- Epigenetic and transcriptional control of classical and basal-like cell states in pancreatic ductal adenocarcinoma.Gastroenterology report · 2026Review
- Lung adenocarcinoma with KRAS-Q61H: clinicopathologic features, diagnostics, and the evolving treatment landscape.Frontiers in oncology · 2026Review
- Integrating network pharmacology, molecular docking, and experimental validation to investigate the therapeutic effects and potential mechanisms of lycopene against pancreatic ductal adenocarcinoma.Frontiers in nutrition · 2026Article
- Identification of Senescence- and Inflammation-Related Genes and Immune Microenvironment Characterization in Intracranial AneurysmsEndocrine, metabolic & immune disorders drug targets · 2026Article
- Cellular Senescence as a Risk Factor in Head and Neck Cancer-Diagnostic and Therapeutic Perspective.Cancers · 2025Review
- Gastrointestinal cancer: molecular pathogenesis and targeted therapy.Molecular biomedicine · 2025Review
350 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
TP53 mutation occurs in 50-75% of human pancreatic ductal adenocarcinomas (PDAC) following an initiating activating mutation in the KRAS gene. These p53 mutations frequently result in expression of a stable protein, p53(R175H), rather than complete loss of protein expression. In this study we elucidate the functions of mutant p53 (Trp53(R172H)), compared to knockout p53 (Trp53(fl)), in a mouse model of PDAC. First we find that although Kras(G12D) is one of the major oncogenic drivers of PDAC, most Kras(G12D)-expressing pancreatic cells are selectively lost from the tissue, and those that remain form premalignant lesions. Loss, or mutation, of Trp53 allows retention of the Kras(G12D)-expressing cells and drives rapid progression of these premalignant lesions to PDAC. This progression is consistent with failed growth arrest and/or senescence of premalignant lesions, since a mutant of p53, p53(R172P), which can still induce p21 and cell cycle arrest, is resistant to PDAC formation. Second, we find that despite similar kinetics of primary tumor formation, mutant p53(R172H), as compared with genetic loss of p53, specifically promotes metastasis. Moreover, only mutant p53(R172H)-expressing tumor cells exhibit invasive activity in an in vitro assay. Importantly, in human PDAC, p53 accumulation significantly correlates with lymph node metastasis. In summary, by using 'knock-in' mutations of Trp53 we have identified two critical acquired functions of a stably expressed mutant form of p53 that drive PDAC; first, an escape from Kras(G12D)-induced senescence/growth arrest and second, the promotion of metastasis.
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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.