{
  "abstract": "Background: The role of mast cells in colorectal cancer (CRC) liver metastasis remains controversial. This study aimed to explore the effect of mast cells on the CRC liver metastasis and the underlying mechanism.\n\nMethods: The bulk-seq, scRNA-seq datasets and clinical samples were integrated to identify the association of mast cells and the SPP1-CD44 signaling and BTG1 with CRC liver metastasis. The effect of mast cells on CRC was determined using co-culture systems and xenograft model. The cell viability, migration, invasion, and epithelial to mesenchymal transition (EMT) were determined. The interaction of BTG1 and JUN was also determined.\n\nResults: The integrated analysis of bulk-seq, scRNA-seq datasets revealed that activated mast cells and downregulation BTG1 expression were associated with CRC liver metastasis, and activated mast cells exhibit enhanced SPP1-CD44 signaling with CRC cells. CRC cell supernatants promote mast cells activation and downregulate BTG1 expression and upregulated SPP1 expression. Conversely, activated mast cells promote CRC cell viability, migration, invasion, and EMT activity via SPP1 secretion. Blocking SPP1 suppress the effect of activated mast cells on CRC cells. Mechanistically, BTG1 acts as a tumor suppressor by directly binding to JUN and promoting its degradation. BTG1 knockdown enhances tumorigenicity in vitro and promoted liver metastasis in vivo, these effects partially reversed by JUN inhibition.\n\nConclusions: Mast cells drive CRC cells liver metastasis through modulation of the BTG1-JUN signaling axis. BTG1 acts as a tumor suppressor in CRC by directly binding to JUN and promoting its degradation, thereby restraining oncogenic signaling.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06367-y.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastrointestinal Surgery, The First People’s Hospital of Nanning/The Fifth Affiliated Hospital of Guangxi Medical University, No. 89 Qixing Road, Nanning, 530021 China",
    "Department of Experimental Research, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Nanning, 530021 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhao-yi Wei"
    },
    {
      "affs": [
        1
      ],
      "name": "Feng Lv"
    },
    {
      "affs": [
        0
      ],
      "name": "Liang Hao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jian-wen Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Bang-li Hu",
      "orcid": "0000-0002-4401-0601"
    },
    {
      "affs": [
        0
      ],
      "name": "Jin-xin Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8a514ymt9z8s6.bib",
  "cited_by": 0,
  "doi": "10.1007/s00018-026-06367-y",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737243/",
  "id": "8a514ymt9z8s6",
  "issns": [
    "1420-682X",
    "1420-9071"
  ],
  "landing_url": "https://doi.org/10.1007/s00018-026-06367-y",
  "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",
      "Original Article"
    ],
    [
      "openalex",
      "2403|Mast cells and histamine"
    ]
  ],
  "openalex": "W7197037910",
  "pdf_url": null,
  "pmcid": "PMC13737243",
  "pmid": "42980805",
  "published": "2026-08-07",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/8a514ymt9z8s6.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:29Z",
      "native_id": "PMC13737243",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00018-026-06367-y"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Mast cells and histamine",
      "subfield": "immunology"
    }
  ],
  "title": "Mast cell–derived SPP1 promotes colorectal cancer liver metastasis by suppressing BTG1-mediated JUN degradation",
  "title_text": "Mast cell–derived SPP1 promotes colorectal cancer liver metastasis by suppressing BTG1-mediated JUN degradation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:29Z",
  "url": "https://research.draconitic.com/paper/8a514ymt9z8s6",
  "venue": "Cellular and Molecular Life Sciences: CMLS",
  "versions": []
}