ArticleThe Journal of experimental medicine2015
IKKβ acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 136 citations in OpenAlex.
- Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue.Physiological genomics · 2016Trial
- Glycolytic cancer-associated fibroblasts orchestrate metabolic remodeling in the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2026Review
- geneSCOPE: gene spatial co-occurrence of pairwise expression.Briefings in bioinformatics · 2026Article
- Navigating the Tumor Microenvironment in Colorectal Liver Metastasis: Barriers to Therapy and Emerging Opportunities.Oncology research · 2026Review
- Cross-talk between cancer-associated fibroblasts and dormant cancer cells: current status and promising therapeutic potential.Cancer cell international · 2025Review
- The emerging role of cancer-associated fibroblasts in hematological malignancies: from their influence on tumor progression and drug resistance to novel therapeutic opportunities.Clinical and experimental medicine · 2025Review
- NF-κB in inflammation and cancer.Cellular & molecular immunology · 2025Review
- Transcriptome Landscape of Cancer-Associated Fibroblasts in Human PDAC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unveiling the link between chronic inflammation and cancer.Metabolism open · 2025Review
- NF-κB signaling and the tumor microenvironment in osteosarcoma: implications for immune evasion and therapeutic resistance.Frontiers in immunology · 2025Review
- Reinventing type 2 immunity in cancer.Nature · 2025Review
- Tumor microenvironment remodeling after neoadjuvant chemoradiotherapy in local advanced rectal cancer revealed by single-cell RNA sequencing.Journal of translational medicine · 2024Article
- YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer.Cancer research · 2024Article
- Tumor Cell Stemness and Stromal Cell Features Contribute to Oral Cancer Outcome Disparity in Black Americans.Cancers · 2024Article
- Mouse Models to Evaluate the Functional Role of the Tumor Microenvironment in Cancer Progression and Therapy Responses.Cold Spring Harbor perspectives in medicine · 2024Review
- NFκB signalling in colorectal cancer: Examining the central dogma of IKKα and IKKβ signalling.Heliyon · 2024Review
- Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression.World journal of gastrointestinal oncology · 2024Review
- Fibroblasts in Orchestrating Colorectal Tumorigenesis and Progression.Cellular and molecular gastroenterology and hepatology · 2024Review
- NF-κB signaling pathway in tumor microenvironment.Frontiers in immunology · 2024Review
- Activation and Functions of Col6a1+ Fibroblasts in Colitis-Associated Cancer.International journal of molecular sciences · 2023Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) comprise one of the most important cell types in the tumor microenvironment. A proinflammatory NF-κB gene signature in CAFs has been suggested to promote tumorigenesis in models of pancreatic and mammary skin cancer. Using an autochthonous model of colitis-associated cancer (CAC) and sporadic cancer, we now provide evidence for a tumor-suppressive function of IKKβ/NF-κB in CAFs. Fibroblast-restricted deletion of Ikkβ stimulates intestinal epithelial cell proliferation, suppresses tumor cell death, enhances accumulation of CD4(+)Foxp3(+) regulatory T cells, and induces angiogenesis, ultimately promoting colonic tumor growth. In Ikkβ-deficient fibroblasts, transcription of negative regulators of TGFβ signaling, including Smad7 and Smurf1, is impaired, causing up-regulation of a TGFβ gene signature and elevated hepatocyte growth factor (HGF) secretion. Overexpression of Smad7 in Ikkβ-deficient fibroblasts prevents HGF secretion, and pharmacological inhibition of Met during the CAC model confirms that enhanced tumor promotion is dependent on HGF-Met signaling in mucosa of Ikkβ-mutant animals. Collectively, these results highlight an unexpected tumor suppressive function of IKKβ/NF-κB in CAFs linked to HGF release and raise potential concerns about the use of IKK inhibitors in colorectal cancer patients.
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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.