ArticleThe Journal of clinical investigation2016
RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- NF-κB inducing kinase (NIK) deletion accelerates KRAS-driven pancreatic cancer in association with tumor microenvironment remodeling.Cell death & disease · 2026Article
- The Significance of CXCL1 in Cancer: An Overview of Molecular Mechanisms.International journal of molecular sciences · 2026Review
- The relationship between CXC chemokines and cellular senescence: from mechanisms to therapy.Biogerontology · 2026Review
- Unveiling the Hub Genes Associated with the Enhanced Effects of Selenium on Pancreas Function in Diabetic Mice.Molecular biotechnology · 2026Article
- c-Rel drives pancreatic cancer metastasis through fibronectin-integrin signaling-induced isolation stress resistance and EMT.Molecular cancer · 2025Article
- Chemotherapy-associated mutational process signature and genomic alterations associated with outcome in metastatic pancreatic cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Loss ofOncotarget · 2025Article
- Unraveling senescence in cancer: mechanistic complexities and therapeutic opportunities.Molecular biology reports · 2025Review
- Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- A decision point between transdifferentiation and programmed cell death priming controls KRAS-dependent pancreatic cancer development.Nature communications · 2025Article
- The senescence-associated secretory phenotype and its physiological and pathological implications.Nature reviews. Molecular cell biology · 2024Review
- FRA1 controls acinar cell plasticity during murine KrasDevelopmental cell · 2024Article
- Non-pituitary growth hormone enables colon cell senescence evasion.Aging cell · 2024Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- NEMO/NF-κB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer.Molecular cancer · 2024Article
- The impact of the senescent microenvironment on tumorigenesis: Insights for cancer therapy.Aging cell · 2024Review
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- Combating PDAC Drug Resistance: The Role of Ref-1 Inhibitors in Accelerating Progress in Pancreatic Cancer Research.Journal of cellular signaling · 2024Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Tumor suppression that is mediated by oncogene-induced senescence (OIS) is considered to function as a safeguard during development of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms that regulate OIS in PDAC are poorly understood. Here, we have determined that nuclear RelA reinforces OIS to inhibit carcinogenesis in the Kras mouse model of PDAC. Inactivation of RelA accelerated pancreatic lesion formation in Kras mice by abrogating the senescence-associated secretory phenotype (SASP) gene transcription signature. Using genetic and pharmacological tools, we determined that RelA activation promotes OIS via elevation of the SASP factor CXCL1 (also known as KC), which activates CXCR2, during pancreatic carcinogenesis. In Kras mice, pancreas-specific inactivation of CXCR2 prevented OIS and was correlated with increased tumor proliferation and decreased survival. Moreover, reductions in CXCR2 levels were associated with advanced neoplastic lesions in tissue from human pancreatic specimens. Genetically disabling OIS in Kras mice caused RelA to promote tumor proliferation, suggesting a dual role for RelA signaling in pancreatic carcinogenesis. Taken together, our data suggest a pivotal role for RelA in regulating OIS in preneoplastic lesions and implicate the RelA/CXCL1/CXCR2 axis as an essential mechanism of tumor surveillance in PDAC.
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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.