{
  "abstract": "Liver-organotropic metastasis occurs in cancers such as uveal melanoma (UM) and pancreatic ductal adenocarcinoma (PDAC) and is a leading cause of mortality at the terminal stage. Colonization is a rate-limiting and converging step in the metastatic cascade. The drivers underlying liver colonization have largely remained elusive. In this report, we hypothesized that pioneer transcription factors (TFs) increase chromatin accessibility and superenhancer (SE) remodeling, which subsequently promote colonization-associated cellular features [e.g., proliferation, survival, cancer stem cells (CSCs), motility] by driving the transcription of the respective SE-associated genes. We tested this hypothesis and discovered that the pioneer TF KLF4 promoted chromatin accessibility and SE remodeling by ATAC-seq and ChIP-seq. Chromatin accessibility and SE remodeling significantly increased the transcription of the SE-associated genes MCL1 and RASGRP3, which consequently promoted proliferation, motility, and metastasis. Furthermore, the upregulation of KLF4 expression in UM cells was promoted by RN7SL2-containing exosomes from surrounding endothelial cells. Analysis of clinical datasets revealed that the overexpression of RIG-I, STAT1, KLF4, and RASGRP3 was individually correlated with shorter metastasis-free survival or overall survival in patients with UM and PDAC. In conclusion, the identification of the exoRN7SL2-STAT1-KLF4-SEs-RASGRP3 signaling axis may help elucidate metastatic colonization through interactions between tumor cells and the endothelial niche and may yield novel and viable therapeutic targets.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.",
    "State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. panjx2@mail.sysu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bei Jin",
      "orcid": "0000-0002-3081-7164"
    },
    {
      "affs": [
        0
      ],
      "name": "Shenglan Liu",
      "orcid": "0000-0002-7306-7922"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongke Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Luo Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dong Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Dai"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingfeng Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Yun Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ping Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qianyun Ye"
    },
    {
      "affs": [
        1
      ],
      "name": "Jingxuan Pan",
      "orcid": "0000-0001-7128-2947"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/34t34kyarderq.bib",
  "cited_by": 0,
  "doi": "10.1038/s41392-026-02876-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13677724",
  "id": "34t34kyarderq",
  "issns": [
    "2095-9907",
    "2059-3635"
  ],
  "landing_url": "https://europepmc.org/article/MED/42894010",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7222872628",
  "pdf_url": "https://europepmc.org/articles/PMC13677724?pdf=render",
  "pmcid": "PMC13677724",
  "pmid": "42894010",
  "published": "2026-10-19",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/34t34kyarderq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42894010",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894010"
    },
    {
      "first_seen": "2026-10-30T13:46:36Z",
      "native_id": "cd90fb70674949eda13b4682c59f0dca",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41392-026-02876-1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Extracellular vesicles in disease",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Endothelial exosomes remodel chromatin accessibility and superenhancer in cancer cells to promote liver metastatic colonization.",
  "title_text": "Endothelial exosomes remodel chromatin accessibility and superenhancer in cancer cells to promote liver metastatic colonization.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:36Z",
  "url": "https://research.draconitic.com/paper/34t34kyarderq",
  "venue": "Signal transduction and targeted therapy",
  "versions": []
}