{
  "abstract": "Cervical cancer remains the fourth most common malignancy among women worldwide, and patients with advanced-stage disease continue to experience poor clinical outcomes despite the availability of targeted therapies. In this study, we investigated the epigenetic role of endothelial cell-specific molecule 1 (ESM1), a soluble proteoglycan, and established an oncogene whose regulatory mechanisms in cervical cancer remain largely unexplored. The epigenetic mechanisms underlying tumor progression remain incompletely understood. Here, we identify ESM1 as a critical epigenetic regulator of cervical cancer malignancy. Integrative analyses of public datasets and clinical specimens revealed that marked ESM1 overexpression correlated with adverse patient prognosis. Functional loss- and gain-of-function studies have demonstrated that ESM1 is essential for maintaining proliferative, clonogenic, migratory, and invasive phenotypes in cervical cancer cells. Transcriptomic profiling revealed that inhibitor of DNA binding 3 (ID3) is a direct downstream tumor suppressor repressed by ESM1. Mechanistically, ESM1 selectively upregulates DNA methyltransferase 3 A (DNMT3A) to induce promoter hypermethylation and transcriptional silencing of ID3. Pharmacological demethylation reactivates ID3 expression and attenuates metastatic capacity. In vivo xenograft and experimental metastasis models validated that ESM1 depletion significantly impaired tumor growth and lung metastasis while increasing ID3 expression. These findings identify the ESM1/DNMT3A/ID3 axis as a novel epigenetic driver of cervical cancer and a potential therapeutic target.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Research, Hsinchu MacKay Memorial Hospital, Hsinchu City, Taiwan",
    "Institute of Biomedical Sciences, MacKay Medical University, New Taipei City, Taiwan",
    "Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan",
    "Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan",
    "Deptartment of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan",
    "School of Medicine, Chung Shan Medical University, Taichung, Taiwan",
    "School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan",
    "Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan",
    "Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Chen-Lin Yu"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Chia-Liang Lin"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Hsiang-Lin Lee"
    },
    {
      "affs": [
        6
      ],
      "name": "Hui-Ling Chiou"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Pei-Ni Chen"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Shun-Fa Yang",
      "orcid": "0000-0002-0365-7927"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Yi-Hsien Hsieh",
      "orcid": "0000-0003-4942-1888"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/87tjf1ara59w0.bib",
  "cited_by": 0,
  "doi": "10.1038/s41420-026-03239-z",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736847/",
  "id": "87tjf1ara59w0",
  "issns": [
    "2058-7716"
  ],
  "landing_url": "https://doi.org/10.1038/s41420-026-03239-z",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7201852949",
  "pdf_url": "https://www.nature.com/articles/s41420-026-03239-z_reference.pdf",
  "pmcid": "PMC13736847",
  "pmid": "42982809",
  "published": "2026-08-07",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/87tjf1ara59w0.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:13Z",
      "native_id": "PMC13736847",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41420-026-03239-z"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Epigenetics and DNA Methylation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "ESM1-mediated DNMT3A suppresses cervical cancer metastasis through epigenetic regulation of ID3 expression",
  "title_text": "ESM1-mediated DNMT3A suppresses cervical cancer metastasis through epigenetic regulation of ID3 expression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:13Z",
  "url": "https://research.draconitic.com/paper/87tjf1ara59w0",
  "venue": "Cell Death Discovery",
  "versions": []
}