ArticleMolecular cancer2010
Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 87 citations in OpenAlex.
- Review
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- Defective N-glycosylation of IL6 induces metastasis and tyrosine kinase inhibitor resistance in lung cancer.Nature communications · 2024Article
- p27 specifically decreases in squamous carcinoma, and mediates NNK-induced transformation of human bronchial epithelial cells.Journal of cellular and molecular medicine · 2024Article
- Autocrine Regulation of Interleukin-6 via the Activation of STAT3 and Akt in Cardiac Myxoma Cells.International journal of molecular sciences · 2024Article
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- Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells.Cell reports · 2024Article
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- MicroRNAs-mediated regulation pathways in rheumatic diseases.Inflammopharmacology · 2023Review
- Trinity of inflammation, innate immune cells and cross-talk of signalling pathways in tumour microenvironment.Frontiers in pharmacology · 2023Review
- Blood transcriptome analysis suggests an indirect molecular association of early life adversities and adult social anxiety disorder by immune-related signal transduction.Frontiers in psychiatry · 2023Article
- TRAIL receptors promote constitutive and inducible IL-8 secretion in non-small cell lung carcinoma.Cell death & disease · 2022Article
- Resveratrol protects human nucleus pulposus cells from degeneration by blocking IL-6/JAK/STAT3 pathway.European journal of medical research · 2021Article
- miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation.Cell death & disease · 2021Article
- Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis.Clinical and experimental immunology · 2021Observational
- Development of the CK-MB-1 trastuzumab-resistant HER2-positive breast cancer cell line and xenograft animal models.Cancer medicine · 2021Article
- Prebiotic Potential and Anti-Inflammatory Activity of Soluble Polysaccharides Obtained from Soybean Residue.Foods (Basel, Switzerland) · 2020Article
- Therapeutic Implication of SOCS1 Modulation in the Treatment of Autoimmunity and Cancer.Frontiers in pharmacology · 2019Review
- Overexpressed HO-1 is associated with reduced STAT3 activation in preeclampsia placenta and inhibits STAT3 phosphorylation in placental JEG-3 cells under hypoxia.Archives of medical science : AMS · 2018Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSpontaneous interleukin-6 (IL-6) production has been observed in various tumors and implicated in the pathogenesis, progression and drug resistance in cancer. However, the regulation of IL-6 autocrine production in cancer cells is not fully understood. IL-6 is auto-regulated in many types of cell. Two of the three major downstream pathways of IL-6, MEK/extracellular signal-related kinase (Erk) pathway and phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, have been shown to regulate IL-6 expression through the activation of AP-1 and NF-κB. However, it is not clear what the role of Janus kinase (Jak) 2/signal transducer and activator of transcription (Stat) 3 pathway. This study was designed to determine the role of Jak2/Stat3 pathway in the regulation of IL-6 autocrine production in cancer cells.
resultsInhibitors of Jak2/Stat3, MEK/Erk and PI3-K/Akt pathways down-regulated IL-6 secretion in the lung adenocarcinoma PC14PE6/AS2 (AS2) cells, which spontaneously secreted IL-6 and possessed constitutively activated Stat3. Transfection with dominant-negative Stat3, Stat3 siRNA, or Stat3 shRNA decreased IL-6 expression in AS2 cells. Conversely, transfection with constitutively-activated Stat3 increased the production of IL-6. In AS2 derived cells, resistance to paclitaxel was positively correlated with Stat3 activation status and the expression of IL-6, which is commonly secreted in drug resistant cancer cells. The pharmacological inhibition of NF-κB, PI3-K/Akt and MEK/Erk and the pharmacological inhibition and genetic inhibition (Stat3 siRNA) of Jak2/Stat3 pathway decreased IL-6 autocrine production in various drug resistant cancer cell lines and similarly decreased IL-6 autocrine production in clinically isolated lung cancer cells.
conclusionsThis study is the first to directly address the role Stat3 plays on the autocrine production of IL-6, which occurs through a positive-feedback loop. Our biochemical and genetic studies clearly demonstrated that Jak2/Stat3, in combination with other IL-6 downstream pathways, contributed frequently and substantially to IL-6 autocrine production in a broad spectrum of cancer cell lines as well as in clinical cancer samples. Our findings suggest that Stat3 could potentially be regulated to suppress IL-6 autocrine production in cancer cells to inhibit the progression of cancer and reduce drug resistance.
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