ArticleCell cycle (Georgetown, Tex.)2017
STAT3-mediated SMAD3 activation underlies Oncostatin M-induced Senescence.
Article in Cell cycle (Georgetown, Tex.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Oncogenic cell fate decision in breast epithelial cells I: growth factors and mechanisms.Research square · 2026Article
- Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.Cancer communications (London, England) · 2026Review
- Nuclear STAT3 expression is associated with favorable prognosis in papillary thyroid carcinoma.European thyroid journal · 2025Article
- Human platelet lysate enhances in vivo activity of CAR-Vδ2 T cells by reducing cellular senescence and apoptosis.Cytotherapy · 2024Article
- Blocking Oncostatin M receptor abrogates STAT3 mediated integrin signaling and overcomes chemoresistance in ovarian cancer.NPJ precision oncology · 2024Article
- Tumor-educated Gr1+CD11b+ cells drive breast cancer metastasis via OSM/IL-6/JAK-induced cancer cell plasticity.The Journal of clinical investigation · 2024Article
- RSK3 switches cell fate: from stress-induced senescence to malignant progression.Journal of experimental & clinical cancer research : CR · 2023Article
- Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders.Molecular neurodegeneration · 2023Review
- The clinical relevance of OSM in inflammatory diseases: a comprehensive review.Frontiers in immunology · 2023Review
- MAPKs in the early steps of senescence implemEMTation.Frontiers in cell and developmental biology · 2023Article
- Cancer Metastasis and Treatment Resistance: Mechanistic Insights and Therapeutic Targeting of Cancer Stem Cells and the Tumor Microenvironment.Biomedicines · 2022Review
- Insulin/IGF-1 signaling promotes immunosuppression via the STAT3 pathway: impact on the aging process and age-related diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- LAMC1 upregulation via TGFβ induces inflammatory cancer-associated fibroblasts in esophageal squamous cell carcinoma via NF-κB-CXCL1-STAT3.Molecular oncology · 2021Article
- The Role of the IL-6 Cytokine Family in Epithelial-Mesenchymal Plasticity in Cancer Progression.International journal of molecular sciences · 2021Review
- Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment.Breast cancer research : BCR · 2021Article
- IL-6 Regulates Hepcidin Expression Via the BMP/SMAD Pathway by Altering BMP6, TMPRSS6 and TfR2 Expressions at Normal and Inflammatory Conditions in BV2 Microglia.Neurochemical research · 2021Article
- Aberrant Induction of a Mesenchymal/Stem Cell Program Engages Senescence in Normal Mammary Epithelial Cells.Molecular cancer research : MCR · 2021Article
- Emerging Perspectives on Leukemia Inhibitory Factor and its Receptor in Cancer.Frontiers in oncology · 2021Review
- Type I interferons and related pathways in cell senescence.Aging cell · 2020Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
Cytokines in the developing tumor microenvironment (TME) can drive transformation and subsequent progression toward metastasis. Elevated levels of the Interleukin-6 (IL-6) family cytokine Oncostatin M (OSM) in the breast TME correlate with aggressive, metastatic cancers, increased tumor recurrence, and poor patient prognosis. Paradoxically, OSM engages a tumor-suppressive, Signal Transducer and Activator of Transcription 3 (STAT3)-dependent senescence response in normal and non-transformed human mammary epithelial cells (HMEC). Here, we identify a novel link between OSM-activated STAT3 signaling and the Transforming Growth Factor-β (TGF-β) signaling pathway that engages senescence in HMEC. Inhibition of functional TGF-β/SMAD signaling by expressing a dominant-negative TGF-β receptor, treating with a TGF-β receptor inhibitor, or suppressing SMAD3 expression using a SMAD3-shRNA prevented OSM-induced senescence. OSM promoted a protein complex involving activated-STAT3 and SMAD3, induced the nuclear localization of SMAD3, and enhanced SMAD3-mediated transcription responsible for senescence. In contrast, expression of MYC (c-MYC) from a constitutive promoter abrogated senescence and strikingly, cooperated with OSM to promote a transformed phenotype, epithelial-mesenchymal transition (EMT), and invasiveness. Our findings suggest that a novel STAT3/SMAD3-signaling axis is required for OSM-mediated senescence that is coopted during the transformation process to confer aggressive cancer cell properties. Understanding how developing cancer cells bypass OSM/STAT3/SMAD3-mediated senescence may help identify novel targets for future "pro-senescence" therapies aiming to reengage this hidden tumor-suppressive response.
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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.