{
  "abstract": "Metabolic reprogramming is increasingly recognized as a key characteristic of intrahepatic cholangiocarcinoma (ICC) initiation and progression. Among these metabolic alterations, glycolysis is central for supporting tumor growth. Elucidating the precise molecular mechanisms of glycolysis in ICC is critical for developing precision therapies. Here, comprehensive integrative analyses revealed that olfactomedin 4 (OLFM4) is upregulated in ICC specimens and is associated with adverse patient outcomes. Mechanistically, OLFM4 promotes ICC progression by recruiting ubiquitin specific peptidase 10 (USP10) to stabilize pyruvate kinase M2 (PKM2). This interaction enhances glycolysis and lactate production, thereby elevating histone lactylation, with a prominent impact on H3K18 lactylation (H3K18la). Consequently, H3K18la positively regulates OLFM4 transcription, establishing a positive glycolysis-histone lactylation feedback loop. Notably, tiliroside, a candidate pharmacological inhibitor of OLFM4, demonstrated antitumor efficacy in ICC. Collectively, these findings support targeting OLFM4 as a promising therapeutic strategy for ICC management.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hepatobiliary Surgery, The First Affiliated Hospital with Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, Jiangsu Province, China.",
    "The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu Province, China.",
    "Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.",
    "Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, China.",
    "Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China.",
    "Jiangsu Provincial Key Laboratory of Chronic Digestive Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, China."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shuochen Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Kai Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Changan Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiao Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Jijun Shan"
    },
    {
      "affs": [
        0
      ],
      "name": "Chang Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruixiang Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yananlan Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiang Chang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wangjie Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaodong Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dong Wang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Changxian Li"
    },
    {
      "affs": [
        0,
        1,
        4,
        5
      ],
      "name": "Xiangcheng Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5bysxqcrbdtk3.bib",
  "cited_by": 0,
  "doi": "10.7150/ijbs.135505",
  "fulltext_url": "https://europepmc.org/articles/PMC13685613",
  "id": "5bysxqcrbdtk3",
  "issns": [
    "1449-2288"
  ],
  "landing_url": "https://europepmc.org/article/MED/42910221",
  "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",
      "2746|Cholangiocarcinoma and Gallbladder Cancer Studies"
    ]
  ],
  "openalex": "W7214682655",
  "pdf_url": "https://europepmc.org/articles/PMC13685613?pdf=render",
  "pmcid": "PMC13685613",
  "pmid": "42910221",
  "published": "2026-09-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5bysxqcrbdtk3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42910221",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42910221"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Cholangiocarcinoma and Gallbladder Cancer Studies",
      "subfield": "surgery"
    }
  ],
  "title": "OLFM4 promotes intrahepatic cholangiocarcinoma progression through a PKM2-glycolysis-histone lactylation feedback loop.",
  "title_text": "OLFM4 promotes intrahepatic cholangiocarcinoma progression through a PKM2-glycolysis-histone lactylation feedback loop.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/5bysxqcrbdtk3",
  "venue": "International journal of biological sciences",
  "versions": []
}