{
  "abstract": "Background: Non-histone acetylation is increasingly implicated in cancer, but the molecular switch governing the context-dependent oncogenic activity of junction plakoglobin (JUP) in gastric cancer (GC) remains unknown.\n\nMethods: Quantitative lysine acetylproteomics and transcriptomic profiling were integrated in 10 paired primary GC and adjacent nontumor tissues. Site-directed JUP mutants, biochemical and molecular assays, functional studies in HGC-27 and MKN-45 cells, xenograft experiments, and analysis of 100 clinical specimens were used to define the regulation, mechanism, and clinical relevance of JUP acetylation.\n\nResults: Acetylproteomics identified 1,054 hyperacetylated proteins, with JUP emerging as a central network hub. JUP acetylation was increased in GC despite unchanged total JUP protein and mRNA levels. Lys326 (K326) was identified as the predominant functional acetylation site. The acetylation-mimetic K326Q mutant prolonged JUP half-life and enhanced colony formation, migration, invasion, and xenograft growth, whereas K326R produced opposing effects. EP300 and SIRT7 were identified as the acetyltransferase and deacetylase, respectively, controlling JUP K326 acetylation. Mechanistically, K326 acetylation promoted nuclear colocalization and association of JUP with TCF4, increased MYC, CCND1, and MMP7 expression, and drove malignant phenotypes that were abolished by TCF4 silencing. In clinical specimens, high JUP K326 acetylation was associated with advanced tumor stage and poorer survival.\n\nConclusion: This study identifies a previously unrecognized EP300/SIRT7-JUP(K326ac)-TCF4 axis that converts JUP from a junctional protein into an oncogenic transcriptional co-regulator. JUP K326 acetylation may serve as a modification-specific biomarker and a tractable therapeutic vulnerability in GC.",
  "abstract_shown": true,
  "affiliations": [
    "Xinxiang Central Hospital",
    "Henan Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Fucheng Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiaxing Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Qiurong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Danyang Chang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lipei Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuhou Shen"
    },
    {
      "affs": [
        1
      ],
      "name": "Haifang Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Xinyue Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Ruxia Sheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Aimin Yue"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6z7jvgtc5hy9t.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1949454",
  "fulltext_url": null,
  "id": "6z7jvgtc5hy9t",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1949454/full",
  "language": null,
  "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": [
    [
      "openalex",
      "2740|Gastric Cancer Management and Outcomes"
    ]
  ],
  "openalex": "W7223037817",
  "pdf_url": "https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1949454/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6z7jvgtc5hy9t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1949454",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1949454/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2234-943X",
      "subfield": "oncology"
    }
  ],
  "title": "Acetylation of JUP at Lys326 promotes gastric cancer progression by enhancing TCF4 transcriptional activity",
  "title_text": "Acetylation of JUP at Lys326 promotes gastric cancer progression by enhancing TCF4 transcriptional activity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/6z7jvgtc5hy9t",
  "venue": "Frontiers in Oncology",
  "versions": []
}