{
  "abstract": "Triple-negative breast cancer (TNBC) lacks effective targeted therapies, and YTHDF proteins are frequently overexpressed in this malignancy, which correlates with adverse prognosis. Through high-throughput drug screening, we identify ellagic acid (EA) as a compound that binds to YTHDF proteins and disrupts their interaction with N6-methyladenosine (m6A)-modified RNAs. Structural and biochemical analyses show that EA targets a conserved, histidine-dependent allosteric site shared among YTHDF paralogs. This interaction induces conformational changes that disrupt m6A recognition and impair RNA binding, effectively inhibiting all three YTHDF proteins without compensatory escape. Phenotypically, EA suppresses TNBC cell proliferation and migration in vitro and in vivo. Mechanistically, EA enhances global mRNA stability, while selectively suppressing translation. In TNBC, EA-induced YTHDF2 inhibition stabilizes PFKFB4 mRNA, thereby increasing PFKFB4 protein, which blocks ubiquitin-dependent degradation of HIF-1α, resulting in BNIP3 induction and ultimately triggering apoptosis and necrosis. Collectively, our work unveils EA as a natural YTHDF inhibitor with compelling therapeutic potential for TNBC.",
  "abstract_shown": true,
  "affiliations": [
    "Jiangsu Key Laboratory of Drug Design and Optimization and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China",
    "School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China",
    "Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China",
    "School of Biomedical Sciences, Hunan University, Changsha 410082, China",
    "Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jianheng Zhou"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuyuan Li"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Xuetao Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhen Zhu"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Tingting Wu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jun Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Siqi Dong"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Weikun Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wenjun Tao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jun Zhou"
    },
    {
      "affs": [
        2
      ],
      "name": "Ke Xu"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Zhengyu Jiang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/49yzjtqm239p9.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103045",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710142/",
  "id": "49yzjtqm239p9",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103045",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|RNA modifications and cancer"
    ]
  ],
  "openalex": "W7213398571",
  "pdf_url": null,
  "pmcid": "PMC13710142",
  "pmid": "42748913",
  "published": "2026-09-16",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/49yzjtqm239p9.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:10Z",
      "native_id": "PMC13710142",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103045"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA modifications and cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Allosteric modulation of YTHDFs by ellagic acid suppresses triple-negative breast cancer via non-canonical activation of the HIF-1α pathway",
  "title_text": "Allosteric modulation of YTHDFs by ellagic acid suppresses triple-negative breast cancer via non-canonical activation of the HIF-1α pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:10Z",
  "url": "https://research.draconitic.com/paper/49yzjtqm239p9",
  "venue": "Cell Reports Medicine",
  "versions": []
}