ArticleBreast cancer research : BCR2010
Differential interleukin-6/Stat3 signaling as a function of cellular context mediates Ras-induced transformation.
Article in Breast cancer research : BCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 81 citations in OpenAlex.
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- The role of endothelin and RAS/ERK signaling in immunopathogenesis-related fibrosis in patients with systemic sclerosis: an updated review with therapeutic implications.Arthritis research & therapy · 2022Review
- IL-6: The Link Between Inflammation, Immunity and Breast Cancer.Frontiers in oncology · 2022Review
- The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer.Journal of personalized medicine · 2021Review
- A Milk-Fat Based Diet Increases Metastasis in the MMTV-PyMT Mouse Model of Breast Cancer.Nutrients · 2021Article
- IL-6 and Soluble Receptors in Overweight and Obese African American Women With and Without Breast Cancer.Biological research for nursing · 2021Article
- Bone marrow adipocytes enhance osteolytic bone destruction by activating 1q21.3(S100A7/8/9-IL6R)-TLR4 pathway in lung cancer.Journal of cancer research and clinical oncology · 2020Article
- Growth pattern can be used as a new characteristic to predict malignancy in breast cancer.Breast cancer (Tokyo, Japan) · 2020Article
- GP130 Cytokines in Breast Cancer and Bone.Cancers · 2020Review
- Synergistic effect of STAT3‑targeted small interfering RNA and AZD0530 against glioblastoma in vitro and in vivo.Molecular medicine reports · 2019Article
- Review
- Antitumor and Anti-Invasive Effect of Apigenin on Human Breast Carcinoma through Suppression of IL-6 Expression.International journal of molecular sciences · 2019Article
- PLA Electrospun Scaffolds for Three-Dimensional Triple-Negative Breast Cancer Cell Culture.Polymers · 2019Article
- Review
- Interleukin-6 and Interferon-α SignalingFrontiers in immunology · 2018Article
- Article
- Mesenchymal Cell Reprogramming in Experimental MPLW515L Mouse Model of Myelofibrosis.PloS one · 2017Article
- STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment.Cancer research · 2016Article
- The Role of the Transcriptional Regulation of Stromal Cells in Chronic Inflammation.Biomolecules · 2015Review
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7 authors at 3 institutions in 2 countries.
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Abstract
introductionTyrosine phosphorylated signal transducer and activator of transcription 3 (pStat3) is present in numerous cancers and is required for mediating tumorigenesis. Autocrine and paracrine interleukin (IL)-6 signaling is the principal mechanism by which Stat3 is persistently phosphorylated in epithelial tumors including breast, lung, colon and gastric cancer. The Ras oncogene mediates cellular transformation without evidence of pStat3 in cultured cells. Recently, however non-tyrosine phosphorylated Stat3 was shown to have a transcriptional activating function, a role in mitochondrial function and to mediate cell migration.. Here we examined the role of Stat3 in Ras mediated transformation.
methodsHa-rasV12 transformed mammary epithelial cells (MCF10A) cells were transduced with a Stat3shRNA, IL-6shRNA and/or treated with inhibitors of Janus kinases (JAKs) to examine the role of the IL-6 signaling pathway in Ras mediated invasion and tumorigenesis.
resultsCellular migration, invasion, anchorage independent growth and tumorigenesis were largely abrogated in the Stat3-reduced cells compared to control cells. Analysis of MCF10A-Ras tumors revealed high levels of pStat3 and interleukin-6. Tumors derived from transgenic MMTV-K-Ras mice were also found to express pStat3 and IL-6. MCF10A-Ras cells, when grown in a three-dimensional Matrigel culture system revealed the appearance of the junctional protein E-Cadherin as a consequence of reducing Stat3 levels or inhibiting Stat3 activity. Decreasing IL-6 levels in the MCF10A-Ras cells abrogated tumorigenesis and reduced cell migration. By isolating Ras-expressing primary tumors and serially passaging these cells in two-dimensional culture led to a decrease in IL-6 and pStat3 levels with the reappearance of E-Cadherin.
conclusionsThe cellular and environmental context can lead to differential IL-6/pStat3 signaling and a dependency on this cytokine and transcription factor for migration, invasion and tumorigenesis.
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