ArticleNature cancer2021
Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 104 citations in OpenAlex.
- Molecular dynamics driving phenotypic divergence among KRAS mutants in pancreatic tumorigenesis.Developmental cell · 2026Article
- Integrative Transcriptional and Chromatin Analyses Reveal Enhancer-Mediated Regulatory Programs Driving Breast Cancer Metastasis.Molecular cancer research : MCR · 2026Article
- Human pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation.Developmental cell · 2026Article
- Article
- Review
- CRISPR screen of human pancreatic cancer xenografts identifies a KLF5 proliferation vulnerability through epigenetic modifiers NCAPD2 and MTHFD1.Molecular cancer · 2026Article
- Transcriptome remodeling of mouse hearts during postnatal cardiac maturation and under proteotoxic stress.Molecular biology reports · 2026Article
- Spatiotemporal control of SMARCA5 by a MAPK-RUNX1 axis distinguishes mutant KRAS-driven pancreatic malignancy from tissue regeneration.Nature cancer · 2026Article
- Loss of SMARCA5 redirects pancreatic tumorigenesis toward a regenerative cell fate.Nature cancer · 2026Article
- Targeting plasticity in the pyrimidine synthesis pathway potentiates macrophage-mediated phagocytosis in pancreatic cancer models.The Journal of clinical investigation · 2025Article
- KLF5 enables dichotomous lineage programs in pancreatic cancer via the AAA+ ATPase coactivators RUVBL1 and RUVBL2.Nature communications · 2025Article
- DNA Damage and Repair in Pancreatic Cancer-The Latest Findings.International journal of molecular sciences · 2025Review
- DR1 activates histone gene expression to maintain pancreatic cancer cell survival through the ATAC complex.Cancer gene therapy · 2025Article
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- Mechanistic Foundations of KRAS-Driven Tumor Ecosystems: Integrating Crosstalk among Immune, Metabolic, Microbial, and Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Self-amplifying NRF2-EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer.Nature cancer · 2025Article
- Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis.Cell research · 2025Article
- TREM2 Depletion in Pancreatic Cancer Elicits Pathogenic Inflammation and Accelerates Tumor Progression via Enriching IL-1βGastroenterology · 2025Article
- The critical role of BMP signaling in gastric epithelial cell differentiation revealed by organoids.Cell regeneration (London, England) · 2025Article
- DNA methylation memory of pancreatic acinar-ductal metaplasia transition state altering Kras-downstream PI3K and Rho GTPase signaling in the absence of Kras mutation.Genome medicine · 2025Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Pancreatic inflammation accelerates mutant Kras-driven tumorigenesis in mice, suggesting high selectivity in the cells that oncogenic Kras transforms, although the mechanisms dictating this specificity are poorly understood. Here we show that pancreatic inflammation is coupled to the emergence of a transient progenitor cell population that is readily transformed in the presence of mutant KrasG12D. These progenitors harbor a proto-oncogenic transcriptional program driven by a transient enhancer network. KrasG12D mutations lock this enhancer network in place, providing a sustained Kras-dependent oncogenic program that drives tumors throughout progression. Enhancer co-option occurs through functional interactions between the Kras-activated transcription factors Junb and Fosl1 and pancreatic lineage transcription factors, potentially accounting for inter-tissue specificity of oncogene transformation. The pancreatic ductal adenocarcinoma cell of origin thus provides an oncogenic transcriptional program that fuels tumor progression beyond initiation, accounting for the intra-tissue selectivity of Kras transformation.
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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.