{
  "abstract": "Purpose: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis and complex tumour microenvironment. We previously demonstrated that doublecortin-like kinase 1 (DCLK1) is associated with epithelial–mesenchymal transition (EMT) in CCA; however, its biological functions and clinical relevance remain unclear. Herein, we elucidated the role of DCLK1 in CCA progression, focusing on its effects on angiogenesis, and evaluated its potential as a prognostic marker.\n\nMethods: We analysed bulk and single-cell RNA sequencing data to characterise DCLK1 expression and function in CCA. Functional validation was performed using conditioned medium from DCLK1-modified CCA cells, as well as endothelial tube formation, migration, and invasion assays. Tumour vascular density was assessed using a xenograft model. We used a human angiogenesis-related antibody array, western blotting, quantitative real-time PCR, and nuclear translocation assays to examine CXCL5 expression and NF-κB pathway activity.\n\nResult: We found that DCLK1 was upregulated in CCA and correlated with advanced disease and poor survival. DCLK1⁺ malignant cells displayed pro-angiogenic features and increased paracrine interaction with endothelial cells. Conditioned medium from DCLK1-overexpressing tumour cells enhanced endothelial tube formation, migration, and invasion, whereas DCLK1 knockout reversed these effects. DCLK1-expressing tumours showed increased vascular density in vivo. Mechanistically, an angiogenesis antibody array and western blotting demonstrated that DCLK1 activated the NF-κB pathway to upregulate CXCL5 expression. Pharmacological inhibition of NF-κB or neutralization of CXCL5 significantly attenuated DCLK1-related pro-angiogenic responses in vitro.\n\nConclusion: DCLK1 activated the NF-κB pathway to upregulate CXCL5 secretion; inhibiting NF-κB or CXCL5 reduced DCLK1-related pro-angiogenic capacity.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00432-026-06568-9.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ziqing Kong"
    },
    {
      "affs": [
        0
      ],
      "name": "Rui Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziwei Liang"
    },
    {
      "affs": [
        0
      ],
      "name": "Guangyu An"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Ge"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6f5w1nvgrf0yg.bib",
  "cited_by": 0,
  "doi": "10.1007/s00432-026-06568-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710486/",
  "id": "6f5w1nvgrf0yg",
  "issns": [
    "0171-5216",
    "1432-1335"
  ],
  "landing_url": "https://doi.org/10.1007/s00432-026-06568-9",
  "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",
      "2746|Cholangiocarcinoma and Gallbladder Cancer Studies"
    ]
  ],
  "openalex": "W7171730135",
  "pdf_url": null,
  "pmcid": "PMC13710486",
  "pmid": "42934373",
  "published": "2026-07-29",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/6f5w1nvgrf0yg.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:27Z",
      "native_id": "PMC13710486",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00432-026-06568-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Cholangiocarcinoma and Gallbladder Cancer Studies",
      "subfield": "surgery"
    }
  ],
  "title": "Integrated multi-omics analysis reveals that tumour cell-intrinsic DCLK1 is associated with an angiogenic tumour microenvironment in cholangiocarcinoma via NF-κB/CXCL5",
  "title_text": "Integrated multi-omics analysis reveals that tumour cell-intrinsic DCLK1 is associated with an angiogenic tumour microenvironment in cholangiocarcinoma via NF-κB/CXCL5",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:27Z",
  "url": "https://research.draconitic.com/paper/6f5w1nvgrf0yg",
  "venue": "Journal of Cancer Research and Clinical Oncology",
  "versions": []
}