{
  "abstract": "Background: The lethality of hepatocellular carcinoma (HCC) stems rom its propensity for distant metastasis and resistance to therapeutic agents, together making it a leading contributor to cancer mortality worldwide. Within the HCC microenvironment, cancer-associated fibroblasts (CAFs) promote tumor progression in part through secreted factors, among which stromal cell-derived factor-1 (SDF-1/CXCL12) signals through its receptor CXCR4, a chemokine receptor that is overexpressed in HCC and correlates with poor prognosis [13,17,38]. Aberrant histone deacetylation is a key epigenetic regulator of HCC progression [20,21,23]. Here, we aimed to investigate the role of fibroblast-derived SDF-1 in modulating histone acetylation through CXCR4 signaling and its impact on HCC cell behavior. Methods: The role of SDF-1 in HCC was investigated using an indirect co-culture model of HepG2 cells and LX2 hepatic stellate cells. SDF-1, CXCR4, HDAC2, and HDAC6 were manipulated by knockdown and overexpression; cell behavior was assessed by Transwell migration, wound healing, CCK-8 viability, and flow cytometric apoptosis assays, and histone acetylation was examined by Western blotting, with the HDAC inhibitor vorinostat used as a comparator. Public single-cell RNA-sequencing data (GSE149614) were used to assess fibroblast SDF-1 enrichment. Results: Our results showed that SDF-1 derived from LX2 cells promoted HepG2 cell migration and proliferation. SDF-1 treatment increased the expression of the mesenchymal markers Snail and Vimentin together with the epithelial marker E-cadherin, a pattern consistent with partial or hybrid epithelial-mesenchymal plasticity rather than a canonical EMT [19,39]. SDF-1 also suppressed global histone acetylation of H2A, H2B, H3, and H4 by upregulating the histone deacetylases HDAC2 and HDAC6. SDF-1 therefore suppresses histone acetylation and enhances HCC cell migration, proliferation, and epithelial-mesenchymal plasticity. Conclusion: This study indicates that fibroblast-derived SDF-1 modulates histone acetylation and regulates HCC cell migration, proliferation, and epithelial-mesenchymal plasticity. Whether the SDF-1/CXCR4 axis is a viable therapeutic target remains to be tested in vivo. Trial registration: Not applicable.",
  "abstract_shown": true,
  "affiliations": [
    "Hepatobiliary Pancreatic Surgery, Jinjiang Municipal Hospital, Quanzhou City, Fujian Province, China; Corresponding author. Hepatobiliary Pancreatic Surgery, Jinjiang Municipal Hospital, Fujian, No. 16, Luoshan Section, Jinguang Road, Jinjiang City, Quanzhou City, Fujian Province, 362200, China.",
    "Quanzhou Medical College, Quanzhou City, Fujian Province, China",
    "Hepatobiliary Pancreatic Surgery, Jinjiang Municipal Hospital, Quanzhou City, Fujian Province, China",
    "Interventional Vascular Surgery, Jinjiang Municipal Hospital, Quanzhou City, Fujian Province, China; Anorectal Surgery, Jinjiang Municipal Hospital, Quanzhou City, Fujian Province, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Siyi Cai"
    },
    {
      "affs": [
        1
      ],
      "name": "Tianshen Xiao"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhongfei Luo"
    },
    {
      "affs": [
        2
      ],
      "name": "Lin Hu"
    },
    {
      "affs": [
        2
      ],
      "name": "Maoyi Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Chunhuai You"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/03w7916jgmfzw.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jrras.2026.102738",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S1687850726005819",
  "id": "03w7916jgmfzw",
  "issns": [
    "2314-7164",
    "1687-8507"
  ],
  "landing_url": "https://doi.org/10.1016/j.jrras.2026.102738",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R895-920"
    ],
    [
      "lcc",
      "TK9001-9401"
    ],
    [
      "openalex",
      "2730|Chemokine receptors and signaling"
    ]
  ],
  "openalex": "W7223477296",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/03w7916jgmfzw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:44:51Z",
      "native_id": "0411c3fe55fe408ab63e660240f6b217",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.jrras.2026.102738"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Chemokine receptors and signaling",
      "subfield": "oncology"
    }
  ],
  "title": "SDF-1 promotes migration, proliferation, and epithelial-mesenchymal plasticity of hepatocellular carcinoma cells via CXCR4-mediated histone deacetylation",
  "title_text": "SDF-1 promotes migration, proliferation, and epithelial-mesenchymal plasticity of hepatocellular carcinoma cells via CXCR4-mediated histone deacetylation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:20:26Z",
  "url": "https://research.draconitic.com/paper/03w7916jgmfzw",
  "venue": "Journal of Radiation Research and Applied Sciences",
  "versions": []
}