ArticleJournal of experimental & clinical cancer research : CR2013
IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancer.
Article in Journal of experimental & clinical cancer research : CR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- The Role of Cytokines in Epithelial-Mesenchymal Transition in Gynaecological Cancers: A Systematic Review.Cells · 2023Pooled it
- Significantly mutated genes and regulatory pathways in SCLC-a meta-analysis.Cancer genetics · 2017Pooled it
- The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Biomarker research · 2026Review
- Impact of interaction between interleukin-27 gene polymorphisms and smoking with susceptibility to non-small cell lung cancer in Chinese Han population.World journal of surgical oncology · 2026Article
- IL-27: A Double-Edged Sword in Immune Regulation via JAK-STAT Orchestration.Journal of immunology research · 2026Review
- The expression and clinical significance of IL-27 and Foxp3 in oral squamous cell carcinoma.BMC cancer · 2025Article
- Harnessing IL-27: challenges and potential in cancer immunotherapy.Clinical and experimental medicine · 2025Review
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Interleukin-27 potentiates CD8+ T-cell-mediated antitumor immunity in chronic lymphocytic leukemia.Haematologica · 2023Article
- Article
- Cytosolic TGM2 promotes malignant progression in gastric cancer by suppressing the TRIM21-mediated ubiquitination/degradation of STAT1 in a GTP binding-dependent modality.Cancer communications (London, England) · 2023Article
- Virtual ChIP-seq: predicting transcription factor binding by learning from the transcriptome.Genome biology · 2022Article
- Review
- Review
- Long Noncoding RNA and Circular RNA: Two Rising Stars in Regulating Epithelial-Mesenchymal Transition of Pancreatic Cancer.Frontiers in oncology · 2022Review
- The Role of the IL-6 Cytokine Family in Epithelial-Mesenchymal Plasticity in Cancer Progression.International journal of molecular sciences · 2021Review
- Epithelial-Mesenchymal Transition in Cancer: A Historical Overview.Translational oncology · 2020Review
- Identification of the Active Compounds and Significant Pathways of Artemisia Annua in the Treatment of Non-Small Cell Lung Carcinoma based on Network Pharmacology.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Cytokine-Induced Guanylate Binding Protein 1 (GBP1) Release from Human Ovarian Cancer Cells.Cancers · 2020Article
- FRA1 contributes to MEK-ERK pathway-dependent PD-L1 upregulation by KRAS mutation in premalignant human bronchial epithelial cells.American journal of translational research · 2020Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundInterleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive and oncogenic activities, respectively. Epithelial-mesenchymal transition (EMT) and angiogenesis are key processes in carcinogenesis. Although IL-27 has been shown to have potent anti-tumor activity in various cancer models, the role of IL-27 in EMT and angiogenesis is poorly understood. In this study, we investigated the role of IL-27 in regulating EMT and angiogenesis through modulation of the STAT pathways in human non-small cell lung carcinoma (NSCLC) cells.
methodsSTAT activation following IL-27 exposure was measured in human NSCLC cell lines. Expression of epithelial (E-cadherin, γ-catenin) and mesenchymal (N-cadherin, vimentin) markers were assessed by Western blot analysis. Production of pro-angiogenic factors (VEGF, IL-8/CXCL8, CXCL5) were examined by ELISA. Cell motility was examined by an in vitro scratch and transwell migration assays. Selective inhibitors of STAT1 (STAT1 siRNAs) and STAT3 (Stattic) were used to determine whether both STAT1 and STAT3 are required for IL-27 mediated inhibition of EMT and secretion of angiogenic factors.
resultsOur results demonstrate that IL-27 stimulation in NSCLC resulted in 1) STAT1 and STAT3 activation in a JAK-dependent manner, 2) development of epithelial phenotypes, including a decrease in the expression of a transcriptional repressor for E-cadherin (SNAIL), and mesenchymal marker (vimentin) with a reciprocal increase in the expression of epithelial markers, 3) inhibition of cell migration, and 4) reduced production of pro-angiogenic factors. STAT1 inhibition in IL-27-treated cells reversed the IL-27 effect with resultant increased expression of Snail, vimentin and the pro-angiogenic factors. The inhibition of STAT3 activation had no effect on the development of the epithelial phenotype.
conclusionIL-27 induces mesenchymal to epithelial transition and inhibits the production of pro-angiogenic factors in a STAT1-dominant pathway. These findings highlight the importance of STAT1 in repressing lung carcinogenesis and describe a new anti-tumor mechanism of IL-27.
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