{
  "abstract": "Background: Although dysregulation of iron metabolism is known to contribute to tumorigenesis, the upstream mechanisms driving iron overload in gastric cancer (GC) remain poorly understood. This research aims to elucidate the oncogenic role of eukaryotic translation initiation factor 3 subunit I (EIF3I) in GC and its impact on iron metabolism.\n\nMethods: EIF3I expression in GC was evaluated using clinical tissue samples and correlated with clinicopathological features. The functional impact of EIF3I on tumor progression was evaluated through both in vitro and in vivo assays. Molecular mechanisms were investigated using protein interaction studies, ubiquitination assays, and transcriptional analyses. A therapeutic peptide targeting EIF3I– was screened and tested in zebrafish and mice models.\n\nResults: EIF3I was significantly overexpressed in GC and associated with aggressive tumor phenotypes. EIF3I depletion suppressed GC cell proliferation and tumor growth, while its overexpression enhanced malignancy. Mechanistically, EIF3I stabilized yes-associated protein 1 (YAP) by directly interacting with it and preventing its ubiquitination and degradation by STUB1. This stabilization promoted YAP nuclear liquid–liquid phase separation and transcriptional activity, leading to increased expression of transferrin receptor 1 (TFR1), and consequent intracellular iron accumulation. Targeting the EIF3I interface on YAP with a screened peptide restored STUB1-mediated YAP degradation and significantly inhibited tumor growth in vitro and in vivo.\n\nConclusions: EIF3I promotes GC progression by stabilizing YAP and reprogramming iron metabolism through the EIF3I–YAP-iron axis. Targeting this interaction represents a promising therapeutic strategy for GC.\n\nSupplementary information: The online version contains supplementary material available at https://doi.org/10.1186/s11658-026-00987-9.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Molecular Target Therapy of Cancer, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei China",
    "Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei China",
    "Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang China",
    "Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, Hubei China",
    "Gucheng People’s Hospital, Hubei University of Arts and Science, Xiangyang, Hubei China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuan Si"
    },
    {
      "affs": [
        0
      ],
      "name": "Dan Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Haitao Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Sicheng Wang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Liang Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiu Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Kangrui Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Ke Xiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangrong Zhan"
    },
    {
      "affs": [
        0
      ],
      "name": "Xu Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingqing Yu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xuewen Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ying Liu",
      "orcid": "0000-0001-7423-5169"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f9r5vdk2zs3w7.bib",
  "cited_by": 0,
  "doi": "10.1186/s11658-026-00987-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737649/",
  "id": "f9r5vdk2zs3w7",
  "issns": [
    "1425-8153",
    "1689-1392"
  ],
  "landing_url": "https://doi.org/10.1186/s11658-026-00987-9",
  "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",
      "Research"
    ],
    [
      "openalex",
      "1307|Hippo pathway signaling and YAP/TAZ"
    ]
  ],
  "openalex": "W7171023254",
  "pdf_url": null,
  "pmcid": "PMC13737649",
  "pmid": "42989073",
  "published": "2026-07-25",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/f9r5vdk2zs3w7.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:47Z",
      "native_id": "PMC13737649",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s11658-026-00987-9"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Hippo pathway signaling and YAP/TAZ",
      "subfield": "cell-biology"
    }
  ],
  "title": "EIF3I reprograms iron metabolism to promote gastric cancer progression by stabilizing YAP",
  "title_text": "EIF3I reprograms iron metabolism to promote gastric cancer progression by stabilizing YAP",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:47Z",
  "url": "https://research.draconitic.com/paper/f9r5vdk2zs3w7",
  "venue": "Cellular & Molecular Biology Letters",
  "versions": []
}