ArticleNature communications2020
Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Mediator subunit MED4 enforces metastatic dormancy in breast cancer.Nature cell biology · 2026Article
- Humanized Antibodies Targeting Ectodomains of IL-6R and GP130 Suppress IL-6/STAT3 Signalling and Tumour Growth in Breast Cancer Models.Journal of cellular and molecular medicine · 2026Article
- Tumor-Associated Macrophages as Therapeutic Targets: Deciphering Interaction Networks and Advancing Clinical Translation.MedComm · 2026Review
- Endothelial activation during the diapedesis of cancer cells: between the kiss of death and therapeutic breakthrough.Cellular & molecular biology letters · 2025Review
- Review
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Article
- Subtherapeutic Dose of Ionizing Radiation Reprograms the Pre-Metastatic Lung Niche, Accelerating Its Formation and Promoting Metastasis.International journal of molecular sciences · 2025Article
- Review
- MCSPNature cancer · 2025Article
- CDO1 phosphorylation is required for IL-6-induced tumor cell proliferation through governing cysteine availability.Cell communication and signaling : CCS · 2025Article
- GTSF1 promotes stemness in uterine carcinosarcoma through CCL1-mediated M1 macrophage aggregation.American journal of cancer research · 2025Article
- Review
- TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma : TGF-β in the microenvironment of multiple myeloma.Annals of hematology · 2024Review
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
- Obesity Arrhythmias: Role of IL-6 Trans-Signaling.International journal of molecular sciences · 2024Review
- Molecular analysis of primary and metastatic sites in patients with renal cell carcinoma.The Journal of clinical investigation · 2024Article
- Lung endothelium exploits susceptible tumor cell states to instruct metastatic latency.Nature cancer · 2024Article
- Development and validation of a nomogram for predicting immune-related pneumonitis after sintilimab treatment.Cancer medicine · 2024Article
Corrections and comments
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Authors and funding
33 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130. Responsiveness to IL6 trans-signals is found to be niche-dependent as bone marrow stromal and endosteal cells down-regulate gp130 in premalignant mammary epithelial cells as opposed to vascular niche cells. PIK3CA activation renders cells independent from IL6 trans-signaling. Consistent with a bottleneck function of microenvironmental DCC control, we find PIK3CA mutations highly associated with late-stage metastatic cells while being extremely rare in early DCCs. Our data suggest that the initial steps of metastasis formation are often not cancer cell-autonomous, but also depend on microenvironmental signals.
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Registered trials
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