{
  "abstract": "Background: Colorectal cancer liver metastasis (CRLM) remains a major cause of mortality in colorectal cancer (CRC), while the upstream molecular mechanisms linking tumor cell adaptation and immune microenvironment remodeling remain poorly understood. Methods: By integrating single-cell RNA sequencing, multi-omics analysis, clinical cohorts, and functional experiments, we investigated the role and mechanism of TCF4 post-translational modification in CRLM progression. Results: We identified O-GlcNAcylated TCF4 as a critical driver of CRLM. TCF4 was significantly upregulated in CRLM and associated with poor prognosis. Mechanistically, OGT-mediated O-GlcNAcylation at Ser163 promoted TCF4 nuclear localization and enhanced its transcriptional activity. O-GlcNAcylated TCF4 directly activated GPX4 transcription, conferring ferroptosis resistance and preserving the malignant characteristics of CRC cells. Furthermore, TCF4 promoted CSF1 secretion, activating the CSF1/CSF1R axis to facilitate TAM recruitment and M2 macrophage polarization, thereby establishing an immunosuppressive metastatic niche. Conclusions: Our study reveals an O-GlcNAcylated TCF4-ferroptosis-immune regulatory axis that coordinates tumor intrinsic adaptation and microenvironmental remodeling during CRLM progression, providing potential therapeutic targets for preventing CRLM.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Laboratory Medicine, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, China.",
    "Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.",
    "Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, China.",
    "Department of Gastrointestinal Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Han Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Jinhao Yu"
    },
    {
      "affs": [
        1
      ],
      "name": "Dong Hou"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiaxin Lin"
    },
    {
      "affs": [
        3
      ],
      "name": "Guangyao Chen",
      "orcid": "0009-0009-9275-4726"
    },
    {
      "affs": [
        1
      ],
      "name": "Bin Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Dongming Lai"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Fanghai Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Hongming Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7w6cctcdkf18e.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18193105",
  "fulltext_url": "https://europepmc.org/articles/PMC13664046",
  "id": "7w6cctcdkf18e",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://europepmc.org/article/MED/42882800",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7214233121",
  "pdf_url": "https://europepmc.org/articles/PMC13664046?pdf=render",
  "pmcid": "PMC13664046",
  "pmid": "42882800",
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7w6cctcdkf18e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42882800",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42882800"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6694",
      "subfield": "oncology"
    }
  ],
  "title": "O-GlcNAcylated TCF4 Drives Ferroptosis Resistance and Tumor-Associated Macrophage Infiltration to Promote Colorectal Cancer Liver Metastasis.",
  "title_text": "O-GlcNAcylated TCF4 Drives Ferroptosis Resistance and Tumor-Associated Macrophage Infiltration to Promote Colorectal Cancer Liver Metastasis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/7w6cctcdkf18e",
  "venue": "Cancers",
  "versions": []
}