{
  "abstract": "Background: Androgen receptor (AR) mutations in prostate cancer mainly cluster in the ligand binding domain (LBD), leading to therapy resistance. However, the biological role of AR in gastric cancer (GC) remains to be explored. We identified the A32C (p.Y11S) mutation was located in NTD and promoted the malignant progression of GC.\n\nMethods: We analyzed 33 kinds of tumors in TCGA database and verified in 65 GC cases. Biological function analysis included proliferation, apoptosis and migration assays. The mechanism was studied by transcriptome map analysis, co-immunoprecipitation and drug inhibition with TAE226 in vitro and in liver metastasis models.\n\nResults: AR A32C mutation significantly enhanced proliferation, anti-apoptotic capacity and G1/S phase transition ability, compared with wild-type AR. The substitution of Y11S site enhanced the binding affinity between AR and YWHAZ, thus establishing a cytoplasmic scaffold, which can spontaneously activate the FAK-PXN axis and downstream PI3K-AKT/ERK pathways. Knockdown of YWHAZ or inhibition of FAK rescued the malignant phenotype. In vivo, MT-AR cells exhibited higher hepatic colonization ability than wild-type cells, and the high activity of FAK persisted in metastatic lesions.\n\nConclusion: The AR A32C mutation is a previously unrecognized oncogenic driver, which can promote the metastasis of GC though YWHAZ mediated ligand independent FAK activation mechanism. These findings extend the research scope of AR mutation biology beyond hormone dependent cancers, and establish that FAK inhibitors based on AR mutation status are suitable for the treatment of AR mutant GC as a precision therapy.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08691-0.",
  "abstract_shown": true,
  "affiliations": [
    "The First Clinical College of China Medical University, Shenyang, China",
    "Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China",
    "National Clinical Research Center for Medical Auxiliary Technology (Laboratory Medicine), Department of Laboratory Medicine, The First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang, Liaoning Province 110001 P.R. China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tianru Ben"
    },
    {
      "affs": [
        0
      ],
      "name": "Lingyu Zhou"
    },
    {
      "affs": [
        1
      ],
      "name": "Zonghao Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiang Jiao"
    },
    {
      "affs": [
        2
      ],
      "name": "Linlin Gao"
    },
    {
      "affs": [
        2
      ],
      "name": "Nan Xia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7v1xbfd9w9nbp.bib",
  "cited_by": 0,
  "doi": "10.1186/s12967-026-08691-0",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711951/",
  "id": "7v1xbfd9w9nbp",
  "issns": [
    "1479-5876"
  ],
  "landing_url": "https://doi.org/10.1186/s12967-026-08691-0",
  "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",
      "2740|Prostate Cancer Treatment and Research"
    ]
  ],
  "openalex": "W7171871840",
  "pdf_url": null,
  "pmcid": "PMC13711951",
  "pmid": "42947132",
  "published": "2026-07-30",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/7v1xbfd9w9nbp.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:38Z",
      "native_id": "PMC13711951",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12967-026-08691-0"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Prostate Cancer Treatment and Research",
      "subfield": "general"
    }
  ],
  "title": "Novel androgen receptor N-terminal mutation drives gastric cancer metastasis via YWHAZ-mediated FAK pathway activation",
  "title_text": "Novel androgen receptor N-terminal mutation drives gastric cancer metastasis via YWHAZ-mediated FAK pathway activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:38Z",
  "url": "https://research.draconitic.com/paper/7v1xbfd9w9nbp",
  "venue": "Journal of Translational Medicine",
  "versions": []
}