ArticleBMC cancer2019
Tumor suppressor HIC1 is synergistically compromised by cancer-associated fibroblasts and tumor cells through the IL-6/pSTAT3 axis in breast cancer.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
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- Tumor Immunosenescence Driven by Chronic Inflammation: Mechanisms, Microenvironment Remodeling and Therapeutic Strategies.Aging and disease · 2025Review
- Identification and experimental validation of prognostic genes related to cytochrome c in breast cancer.Frontiers in genetics · 2025Article
- IL-6 is associated with poor seizure control in low-grade glioma patients undergoing primary resection.iScience · 2024Article
- Increased expression of SSEA-4 on TKI-resistant non-small cell lung cancer with EGFR-T790M mutation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Crosstalk and plasticity driving between cancer-associated fibroblasts and tumor microenvironment: significance of breast cancer metastasis.Journal of translational medicine · 2023Review
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- Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4Cell reports · 2023Article
- The Mechanism of DNA Methylation and miRNA in Breast Cancer.International journal of molecular sciences · 2023Review
- The importance of cancer-associated fibroblasts in targeted therapies and drug resistance in breast cancer.Frontiers in oncology · 2023Review
- Long noncoding RNA MEG3 inhibits oral squamous cell carcinoma progression via GATA3.FEBS open bio · 2023Article
- Effect of Poly(methacrylic acid) on the Cytokine Level in an In Vivo Tumor Model.Molecules (Basel, Switzerland) · 2022Article
- Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer.Frontiers in pharmacology · 2022Article
- Proline oxidase silencing inhibits p53-dependent apoptosis in MCF-7 breast cancer cells.Amino acids · 2021Article
- Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.Signal transduction and targeted therapy · 2021Review
- Inflammatory Cytokines in Cancer: Comprehensive Understanding and Clinical Progress in Gene Therapy.Cells · 2021Review
- The Tumor Microenvironment of Primitive and Metastatic Breast Cancer: Implications for Novel Therapeutic Strategies.International journal of molecular sciences · 2020Review
- The Role of Mesenchymal Stem Cells in Modulating the Breast Cancer Microenvironment.Cell transplantationReview
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundInterleukin-6 (IL-6) is commonly highly secreted in the breast cancer (BrCA) microenvironment and implicated in disease development. In this study, we aimed to determine the role of the IL-6/pSTAT3/HIC1 axis in the breast cancer microenvironment, including in cancer-associated fibroblasts (CAFs) and breast cancer cells.
methodsStromal fibroblasts from the breast cancer tissue were isolated, and the supernatants of the fibroblasts were analyzed. Recombinant human IL-6 (rhIL-6) was applied to simulate the effect of CAF-derived IL-6 to study the mechanism of HIC1 (tumor suppressor hypermethylated in cancer 1) downregulation. IL-6 was knocked down in the high IL-6-expressing BrCA cell line MDA-MB-231, which enabled the investigation of the IL-6/pSTAT3/HIC1 axis in the autocrine pathway.
resultsIncreased IL-6 was found in the supernatant of isolated CAFs, which suppressed HIC1 expression in cancer cells and promoted BrCA cell proliferation. After stimulating the BrCA cell line SK-BR-3 (where IL-6R is highly expressed) with rhIL-6, signal transducers and activators of transcription 3 (STAT3) was found to be phosphorylated and HIC1 decreased, and a STAT3 inhibitor completely rescued HIC1 expression. Moreover, HIC1 was restored upon knocking down IL-6 expression in MDA-MB-231 cells, accompanied by a decrease in STAT3 activity.
conclusionsThese findings indicate that IL-6 downregulates the tumor suppressor HIC1 and promotes BrCA development in the tumor microenvironment through paracrine or autocrine signaling.
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