ArticleNature communications2015
Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers.
What it found
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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
228 citing papers in PubMed, 345 citations in OpenAlex.
- Trial
- Unleashing the power of DNA-encoded libraries for challenging targets in drug discovery.Pharmaceutical science advances · 2026Review
- Treg-derived exosomal miR-146a orchestrates bidirectional Treg-CAF crosstalk to sustain immunosuppressive tumor microenvironments.Medical oncology (Northwood, London, England) · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Article
- From inflammation to malignancy: the dynamic evolution of cancer-associated fibroblasts in IBD-CRC.Neoplasia (New York, N.Y.) · 2026Review
- Radiation-Induced Alterations in Cancer-Associated Fibroblasts: Drivers of Tumor Radioresistance and Therapeutic Targets.Biomolecules · 2026Review
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- The extracellular matrix: structure, composition, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- TRKB-based signature identifies high-risk squamous cell carcinoma cases and TRKB blockade reprograms tumor and stromal cells toward suppressive phenotypes.Journal of biomedical science · 2026Article
- Cancer-associated fibroblasts in head and neck tumours: signalling networks and therapeutic implications with insights from vestibular schwannoma.Frontiers in cell and developmental biology · 2026Review
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- lncDILC Downregulation in Liver Cancer-Associated Fibroblasts Drives Pro-Invasive Conversion via a miR-6071-ZNF395 Axis.Cancer science · 2026Article
- Cancer-associated fibroblasts at the crossroads of tumor progression and therapy resistance: from heterogeneity to precision reprogramming.Journal of the Egyptian National Cancer Institute · 2025Review
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Periostin: A matricellular protein with a multifaceted role in tumorigenesis (Review).International journal of molecular medicine · 2025Review
- Significance of Epigenetic Alteration in Cancer-Associated Fibroblasts on the Development of Carcinoma.International journal of molecular sciences · 2025Review
- Crosstalk between heterogeneous cancer-associated fibroblast subpopulations and the immune system in breast cancer: key players and promising therapeutic targets.Journal of experimental & clinical cancer research : CR · 2025Review
- Article
168 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Carcinoma-associated fibroblasts (CAF) mediate the onset of a proinvasive tumour microenvironment. The proinflammatory cytokine LIF reprograms fibroblasts into a proinvasive phenotype, which promotes extracellular matrix remodelling and collective invasion of cancer cells. Here we unveil that exposure to LIF initiates an epigenetic switch leading to the constitutive activation of JAK1/STAT3 signalling, which results in sustained proinvasive activity of CAF. Mechanistically, p300-histone acetyltransferase acetylates STAT3, which, in turn, upregulates and activates the DNMT3b DNA methyltransferase. DNMT3b methylates CpG sites of the SHP-1 phosphatase promoter, which abrogates SHP-1 expression, and results in constitutive phosphorylation of JAK1. Sustained JAK1/STAT3 signalling is maintained by DNA methyltransferase DNMT1. Consistently, in human lung and head and neck carcinomas, STAT3 acetylation and phosphorylation are inversely correlated with SHP-1 expression. Combined inhibition of DNMT activities and JAK signalling, in vitro and in vivo, results in long-term reversion of CAF-associated proinvasive activity and restoration of the wild-type fibroblast phenotype.
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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.