{
  "abstract": "Prostate cancer (PCa) progression is accompanied by profound alterations in cell-extracellular matrix (ECM) adhesion, nuclear architecture and mechanical adaptability, yet the molecular mechanisms linking these processes remain poorly understood. Hemidesmosomes (HDs), formed by 6{beta}4-integrins, anchor epithelial cells to the basement membrane and couple extracellular forces to the intermediate filament (IF) cytoskeleton. Here, we identify a previously unrecognized tumor-suppressive function of {beta}4-integrins in preserving nuclear integrity in prostate epithelial cells. Loss of {beta}4-integrins disrupted the cytokeratin-5 network and its coupling to the nucleus, leading to nuclear softening, lamin remodeling, reduced heterochromatin content and enhanced confined migration. Unexpectedly, proximity-labeling proteomics revealed that {beta}4-integrins engage nuclear pore complex (NPC) components in an 6-independent manner, particularly upon HD disassembly. Selected interactions were validated using proximity ligation and co-immunoprecipitation assays. {beta}4-integrin loss was associated with enlarged nuclear pores and aberrant nucleocytoplasmic transport, including nuclear accumulation of YAP1. Consistent with these findings, reduced {beta}4-integrin expression in a large PCa tissue cohort correlated with altered nuclear morphology, adverse clinicopathological features, metastatic progression, and poor patient survival. Collectively, our study establishes {beta}4-integrins as a critical molecular link between cell-ECM adhesion, nuclear mechanics and genome integrity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "name": "A. Schmidt"
    },
    {
      "name": "R. Wei"
    },
    {
      "name": "P. Nastaly"
    },
    {
      "name": "M. Mehnaz-Enamul"
    },
    {
      "name": "A. Agashe"
    },
    {
      "name": "M. Rychlowski"
    },
    {
      "name": "K. Bury"
    },
    {
      "name": "S. Koivusalo"
    },
    {
      "name": "Q. Zhang"
    },
    {
      "name": "C. Frascogna"
    },
    {
      "name": "C. F. Natale"
    },
    {
      "name": "X. Yang"
    },
    {
      "name": "A. Jarmakowicz"
    },
    {
      "name": "A. Ahtikoski"
    },
    {
      "name": "M. Vaarala"
    },
    {
      "name": "X. Liu"
    },
    {
      "name": "K. Ruckemann-Dziurdzinska"
    },
    {
      "name": "M. Varjosalo"
    },
    {
      "name": "E. Bryl"
    },
    {
      "name": "A. Nain"
    },
    {
      "name": "G.-H. Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "T. Wenta"
    },
    {
      "name": "A. Manninen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/05n8dxgvg5nkz.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748477",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748477v1.full",
  "id": "05n8dxgvg5nkz",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748477v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2723|Cell Adhesion Molecules Research"
    ]
  ],
  "openalex": "W7207697739",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748477v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/05n8dxgvg5nkz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:37Z",
      "native_id": "10.64898/2026.09.01.748477",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748477v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "β4-integrins safeguard nuclear mechanics to suppress prostate cancer progression",
  "title_text": "β4-integrins safeguard nuclear mechanics to suppress prostate cancer progression",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:37Z",
  "url": "https://research.draconitic.com/paper/05n8dxgvg5nkz",
  "venue": "bioRxiv",
  "versions": []
}