{
  "abstract": "Background: Vaccinia-related kinase 2 (VRK2) is involved in multiple cancers, but its role in the metastasis of hepatocellular carcinoma (HCC) is largely unknown. The regulatory mechanisms underlying the abnormally low expression of the tight junction protein Zonula occludens-1 (ZO-1) in HCC also remain unclear. This study aimed to investigate the function of VRK2 in HCC metastasis and the underlying molecular mechanisms.\n\nMethods: We examined VRK2 expression in HCC tissues using the GEPIA database, immunohistochemistry, western blotting and analyzed its correlation with patient prognosis. Gain- and loss-of-function approaches were employed to assess the effects of VRK2 on HCC cell invasion and metastasis in vitro and in vivo . Isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis, co-immunoprecipitation, phosphoproteomic mass spectrometry, and autophagic flux assays were performed to elucidate the molecular mechanisms.\n\nResults: VRK2 was markedly overexpressed in HCC, and high VRK2 expression was associated with poor overall survival and disease-free survival. Silencing VRK2 decreased HCC cell invasion and metastasis in vitro and in vivo , whereas VRK2 overexpression increased them. Mechanistically, VRK2 directly phosphorylated Autophagy-related 5 (ATG5) at serine 106, enhancing its interaction with Ubiquitin-specific peptidase 13 (USP13) and protecting ATG5 from ubiquitin-dependent proteasomal degradation. The stabilization of ATG5 activated autophagy, which subsequently promoted the degradation of the tight junction protein ZO-1, leading to disruption of cell-cell adhesion and enhanced metastatic capacity. The VRK2-ATG5-autophagy-ZO-1 regulatory axis was validated in clinical HCC tissue specimens.\n\nConclusions: Our findings identify VRK2 as a novel promoter of HCC metastasis through phosphorylation-mediated stabilization of ATG5 and subsequent autophagy-dependent degradation of ZO-1. This study reveals VRK2 as a potential prognostic biomarker and therapeutic target for metastatic HCC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Thyroid Surgery, Second Affiliated Hospital School of Medicine, Zhejiang University",
    "Department of Interventional Radiology and Vascular Surgery, Ganzhou Key Laboratory of Interventional Medicine, Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People’s Hospital)",
    "Center for Medical Research and Innovation in Digestive System Tumors, Minstry of Education",
    "Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mao Ye"
    },
    {
      "affs": [
        1
      ],
      "name": "Baoliang Zhong"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingying Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Binglong Bai"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Hengqing Zhu"
    },
    {
      "affs": [
        3
      ],
      "name": "Jiangtao Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/53h9mm4q16zxv.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1988374",
  "fulltext_url": null,
  "id": "53h9mm4q16zxv",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1988374/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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/53h9mm4q16zxv.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:46Z",
      "native_id": "10.3389/fonc.2026.1988374",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1988374/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2234-943X",
      "subfield": "oncology"
    }
  ],
  "title": "VRK2 promotes HCC metastasis by enhancing autophagy-mediated degradation of ZO-1",
  "title_text": "VRK2 promotes HCC metastasis by enhancing autophagy-mediated degradation of ZO-1",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:26Z",
  "url": "https://research.draconitic.com/paper/53h9mm4q16zxv",
  "venue": "Frontiers in Oncology",
  "versions": []
}