ArticleOncotarget2016
The inflammatory/cancer-related IL-6/STAT3/NF-κB positive feedback loop includes AUF1 and maintains the active state of breast myofibroblasts.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 107 citations in OpenAlex.
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- Molecular mechanisms of acute inflammation: systemic responses and kidney-specific pathophysiology.Function (Oxford, England) · 2026Review
- Chemical diversity and biological activities of marine sponges from the genusFrontiers in pharmacology · 2026Review
- Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses.Oncoimmunology · 2025Article
- Hypoxia-induced secretory autophagy in cancer-associated fibroblasts promotes ECM remodelling through serglycin secretion in oral squamous cell carcinoma.Clinical and translational medicine · 2025Article
- Optimizing Membrane Composition With C15 and Choline: A Novel Hypothesis to Mitigate Cancer Risk.Cureus · 2025Review
- Insights on inflammatory pathways and their cross-talk: a comprehensive review on asthma.Molecular biology reports · 2025Review
- Virally encoded interleukin-6 (vIL-6) coordinates with human IL-6 to modulate cytokine expression during KSHV infection.bioRxiv : the preprint server for biology · 2025Article
- Expression and clinical significance of AUF1 and HIF-1α in papillary thyroid carcinoma.World journal of surgical oncology · 2025Article
- E2F1 activates breast stromal fibroblasts and promotes their paracrine pro-carcinogenic effects.Scientific reports · 2025Article
- Bruton's tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax.Blood cancer journal · 2025Article
- Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential.Frontiers in immunology · 2025Review
- The role of transcription factors in the crosstalk between cancer-associated fibroblasts and tumor cells.Journal of advanced research · 2025Review
- Virus-induced brain pathology and the neuroinflammation-inflammation continuum: the neurochemists view.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- An Update onMicroorganisms · 2024Review
- Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis.Clinical proteomics · 2024Article
- Effect ofVeterinary world · 2024Article
- Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells.International journal of molecular sciences · 2024Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The IL-6/STAT3/NF-κB positive feedback loop links inflammation to cancer and maintains cells at a transformed state. Similarly, cancer-associated myofibroblats remains active even in absence of cancer cells. However, the molecular basis of this sustained active state remains elusive. We have shown here that breast cancer cells and IL-6 persistently activate breast stromal fibroblasts through the stimulation of the positive IL-6/STAT3/NF-κB feedback loop. Transient neutralization of IL-6 in culture inhibited this signaling circuit and reverted myofibrobalsts to a normalized state, suggesting the implication of the IL-6 autocrine feedback loop as well. Importantly, the IL-6/STAT3/NF-κB pro-inflammatory circuit was also active in cancer-associated fibroblasts isolated from breast cancer patients. Transient inhibition of STAT3 by specific siRNA in active fibroblasts persistently reduced the level of the RNA binding protein AUF1, blocked the loop and normalized these cells. Moreover, we present clear evidence that AUF1 is also part of this positive feedback loop. Interestingly, treatment of breast myofibroblasts with caffeine, which has been previously shown to persistently inhibit active breast stromal fibroblasts, blocked the positive feedback loop through potent and sustained inhibition of STAT3, AKT, lin28B and AUF1. These results indicate that the IL-6/STAT3/NF-κB positive feedback loop includes AUF1 and is responsible for the sustained active status of cancer-associated fibroblasts. We have also shown that normalizing myofibroblasts, which could be of great therapeutic value, is possible through the inhibition of this procarcinogenic circuit.
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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.