{
  "abstract": "Background\n\nChronic inflammation exerts paradoxical effects in breast cancer, inducing growth arrest while sustaining tumor progression. However, how autocrine and paracrine inflammatory cytokine induced senescence integrates with tumor-promoting behaviour remains unclear. Here, we identify a reciprocal IL-1β/IL-6 circuit that links inflammatory cues, epigenetic remodeling and cytokine induced senescence in luminal breast cancer cells.Methods\n\nFollowing treatment with IL-1β and IL-6, MCF-7 cells were examined using cell-cycle, apoptosis, reactive oxygen species flow cytometry assays, and senescence assays; RNA sequencing; global DNA methylation quantification; methylation-specific PCR; ChIP-qPCR for histone marks; cytokine ELISA; and western blotting for DNMTs and STAT3/AKT/NF-κB signaling proteins. The kinetics of IL-1β and IL-6 signaling were examined using receptor antagonism and pharmacological inhibition.Results\n\nIL-1β induced senescence characterized by G₀/G₁ arrest, elevated SA-β-gal activity, ROS accumulation and absence of apoptosis. Transcriptomic profiling revealed cell-cycle regulator repression, enrichment of senescence-associated signatures and a pro-inflammatory secretory phenotype. Mechanistically, IL-1β induced increased DNMT1 and DNMT3A expression, elevated global DNA methylation, induced promoter-specific DNA methylation (IL-15, HMGB2) and histone mark remodeling (IL-6, IL1RN, BCL2,BAX) at inflammatory, senescence, and apoptotic loci. IL-1 receptor antagonism attenuated these effects. IL-6 induced downstream of IL-1β, in turn activated STAT3, increased DNMT1 and DNMT3B expression, amplified IL-1β expression and tumor-promoting phenotypes, while sustaining the IL-1β induced senescence state. IL-6R blockade disrupted this axis and reduced tumor-promoting effects.Conclusion\n\nAn IL-1β/IL-6 inflammatory loop drives epigenetic remodeling associated with cytokine induced senescence while promoting tumor-supportive signaling. IL-1β initiates the senescence program, whereas IL-6 reinforces and sustains this state through STAT3/DNMT signaling, highlighting inflammatory cytokine signaling pathways as potential therapeutic targets for breast cancer therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cellular and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, India. Satyajit.pereira@learner.manipal.edu.",
    "Department of Cellular and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, India.",
    "Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.",
    "SDM Centre for Cellular and Molecular Sciences, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara (SDM) University, Dharwad, Karnataka, 580009, India.",
    "Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, India.",
    "SDM Centre for Cellular and Molecular Sciences, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara (SDM) University, Dharwad, Karnataka, 580009, India. ksatyamoorthy@sdmuniversity.edu.in."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Satyajit Dey Pereira",
      "orcid": "0000-0003-1089-0433"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Kanaka Sai Ram Padam",
      "orcid": "0000-0001-5983-0066"
    },
    {
      "affs": [
        3
      ],
      "name": "Padival Shruptha",
      "orcid": "0009-0000-6748-3412"
    },
    {
      "affs": [
        1
      ],
      "name": "Aditi Atreya"
    },
    {
      "affs": [
        4
      ],
      "name": "Manjunath B Joshi",
      "orcid": "0000-0002-1310-5480"
    },
    {
      "affs": [
        5
      ],
      "name": "Kapaettu Satyamoorthy",
      "orcid": "0000-0002-2368-5490"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1b2mx108cyt6c.bib",
  "cited_by": 0,
  "doi": "10.1007/s00011-026-02391-7",
  "fulltext_url": "https://europepmc.org/articles/PMC13676678",
  "id": "1b2mx108cyt6c",
  "issns": [
    "1023-3830",
    "1420-908X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42892641",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Telomeres, Telomerase, and Senescence"
    ]
  ],
  "openalex": "W7222803794",
  "pdf_url": "https://europepmc.org/articles/PMC13676678?pdf=render",
  "pmcid": "PMC13676678",
  "pmid": "42892641",
  "published": "2026-10-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1b2mx108cyt6c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42892641",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42892641"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Telomeres, Telomerase, and Senescence",
      "subfield": "physiology"
    }
  ],
  "title": "IL-1β/IL-6 inflammatory crosstalk drives DNA methylation and histone remodeling associated with cytokine induced senescence in luminal breast cancer.",
  "title_text": "IL-1β/IL-6 inflammatory crosstalk drives DNA methylation and histone remodeling associated with cytokine induced senescence in luminal breast cancer.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/1b2mx108cyt6c",
  "venue": "Inflammation research : official journal of the European Histamine Research Society ... [et al.]",
  "versions": []
}