ArticleNeoplasia (New York, N.Y.)2013
The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis.
Article in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 311 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
311 citing papers in PubMed, 1 synthesis or guideline pooled it, 497 citations in OpenAlex.
- Therapeutic targeting of STAT3 pathways in pancreatic adenocarcinoma: A systematic review of clinical and preclinical literature.PloS one · 2021Pooled it
- A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer.Cancer chemotherapy and pharmacology · 2022Trial
- A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Trial
- Addressing the Limits of Emx2 Therapy of Glioblastoma Multiforme by Transgene Insulation and Epigenetic Pharmacological Intervention.Biomedicines · 2026Article
- Discovery of CDK8/19 inhibitors as lead compounds for IL-6-dependent lymphoma enabled by the formal synthesis of cortistatin A.Science advances · 2026Article
- Remodeling the Immune Landscape: How Obesity-Induced SASPs Create a Pro-Tumorigenic Niche.Current obesity reports · 2026Review
- Programmed cell death and metastatic evolution in breast cancer: the role of anoikis, necroptosis, and ferroptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- EGFR deletion in myeloid cells reprograms the immunosuppressive landscape of colorectal cancer.Cell death and differentiation · 2026Article
- Macrophages in lung cancer: principal factors, regulatory mechanisms, and therapeutic opportunities: a narrative review.Translational lung cancer research · 2026Review
- Homeobox A10 in gastrointestinal malignancies: unraveling metastatic mechanisms and novel therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Exosomal 3'tiRNA-PheGAA and interleukin-6 as novel biomarkers for non-invasive detection of NSCLC.Discover oncology · 2026Article
- Spatially controlled tenascin-C accumulation contributes to inflammatory disease persistence in giant cell aortitis.JCI insight · 2026Article
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Tumor Cells as Architects of Immune Refractoriness: Dismantling Intrinsic Programs of Tumor Cells for Clinical Translation.Immune network · 2026Review
- IL-6R blockade with tocilizumab disrupts pericyte- and tumor cell-driven IL-6/STAT3 signaling, enhancing docetaxel efficacy in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Exercise-modulated IL-6 in cancer cachexia: molecular mechanisms and therapeutic potential.Journal of translational medicine · 2026Review
- Article
- Fibroblast STAT3 Activation Drives Organ-Specific Premetastatic Niche Formation.Cancer research · 2026Article
- Development and Validation of an m6A-Derived Prognostic Signature in Lung Adenocarcinoma.Journal of Cancer · 2026Article
- Orchestrating the pre-metastatic niche: roles of stromal mediators and immune cells in metastatic progression and therapeutic targeting.Frontiers in immunology · 2026Review
251 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 10 institutions in 3 countries.
Funding
Abstract
We have investigated the importance of interleukin-6 (IL-6) in promoting tumor growth and metastasis. In human primary breast cancers, increased levels of IL-6 were found at the tumor leading edge and positively correlated with advanced stage, suggesting a mechanistic link between tumor cell production of IL-6 and invasion. In support of this hypothesis, we showed that the IL-6/Janus kinase (JAK)/signal transducer and activator of transcription 3 (Stat3) pathway drives tumor progression through the stroma and metastatic niche. Overexpression of IL-6 in tumor cell lines promoted myeloid cell recruitment, angiogenesis, and induced metastases. We demonstrated the therapeutic potential of interrupting this pathway with IL-6 receptor blockade or by inhibiting its downstream effectors JAK1/2 or Stat3. These clinically relevant interventions did not inhibit tumor cell proliferation in vitro but had profound effects in vivo on tumor progression, interfering broadly with tumor-supportive stromal functions, including angiogenesis, fibroblast infiltration, and myeloid suppressor cell recruitment in both the tumor and pre-metastatic niche. This study provides the first evidence for IL-6 expression at the leading edge of invasive human breast tumors and demonstrates mechanistically that IL-6/JAK/Stat3 signaling plays a critical and pharmacologically targetable role in orchestrating the composition of the tumor microenvironment that promotes growth, invasion, and metastasis.
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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.