ArticleCancer cell2012
KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma.
Article in Cancer cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 333 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
333 citing papers in PubMed, 1 synthesis or guideline pooled it, 516 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Chemopreventive Effect of Bitter Melon (Momordica charantia) Juice on Pancreatic Carcinogenesis in LSL-KrasMolecular carcinogenesis · 2026Article
- Oncogenic RAS as an adaptive signaling ecosystem: context-dependent vulnerabilities and resistance-informed therapeutic design.Experimental hematology & oncology · 2026Review
- Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses.Molecular therapy. Oncology · 2026Article
- PARP7 inhibitors enhance the immunogenic effects of radiation in pancreatic cancer cells.Molecular therapy. Oncology · 2026Article
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- NF-κB inducing kinase (NIK) deletion accelerates KRAS-driven pancreatic cancer in association with tumor microenvironment remodeling.Cell death & disease · 2026Article
- The oncogenic signalosome: SQSTM1/p62 as a master integrator of signaling, metabolism, and autophagy in cancer.Toxicological research · 2026Review
- Mutant KRAS promotes NF-κB driven CCL20 chemokine expression in pancreatic ductal adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- Interleukin-1β as target to induce synthetic lethality in KRAS mutant biliary tract cancer.Clinical and molecular hepatology · 2026Article
- RAS signaling and remodeling of the immune microenvironment in pancreatic ductal adenocarcinoma: implications of emerging RAS-targeted therapy.Frontiers in cell and developmental biology · 2026Review
- P62 in colorectal cancer: from inflammation suppression to cancer promotion.Frontiers in immunology · 2026Review
- Integrative Transcriptomic Analysis Identifies a Key Candidate Gene Bridging Inflammation and DNA Repair in Endometriosis.Stem cells international · 2026Article
- CCR-CCL axes as key upstream influencers of pancreatic ductal adenocarcinoma: CCR2-CCL2, CCR5-CCL5, CCR4-CCL17/22, CCR6-CCL20, CCR7-CCL19/21.Frontiers in immunology · 2026Review
- Sequestosome-1/p62 Mediates TLR4-Induced Inflammatory Program in Dendritic Cells Under Normoxic and Hypoxic Conditions.Cellular and molecular life sciences : CMLS · 2025Article
- Proteome-wide Mendelian randomization and colocalization analysis uncovers druggable targets for lung cancer across multiple phenotypes and complications.Discover oncology · 2025Article
- Pancreatic Cancer and Diabetes: Insights, Hypotheses, and Next Steps.International journal of molecular sciences · 2025Review
- CAR-Macrophage Cell Therapy: A New Era of Hope for Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- ALDH1A3 promotes aggressive basal-like pancreatic cancer through an AP-1/RUNX2 enhancer network.Oncogene · 2025Article
- Epithelial Ikkβ deletion modulates immune responses and the IFNγ/CXCL9 axis during early esophageal carcinogenesis.Carcinogenesis · 2025Article
273 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Constitutive Kras and NF-κB activation is identified as signature alterations in pancreatic ductal adenocarcinoma (PDAC). However, how NF-κB is activated in PDAC is not yet understood. Here, we report that pancreas-targeted IKK2/β inactivation inhibited NF-κB activation and PDAC development in Kras(G12D) and Kras(G12D);Ink4a/Arf(F/F) mice, demonstrating a mechanistic link between IKK2/β and Kras(G12D) in PDAC inception. Our findings reveal that Kras(G12D)-activated AP-1 induces IL-1α, which, in turn, activates NF-κB and its target genes IL-1α and p62, to initiate IL-1α/p62 feedforward loops for inducing and sustaining NF-κB activity. Furthermore, IL-1α overexpression correlates with Kras mutation, NF-κB activity, and poor survival in PDAC patients. Therefore, our findings demonstrate the mechanism by which IKK2/β/NF-κB is activated by Kras(G12D) through dual feedforward loops of IL-1α/p62.
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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.