{
  "abstract": "Despite the significant clinical value of bevacizumab in treating advanced ovarian cancer (OC), acquired resistance to treatment remains a critical challenge. Bevacizumab therapy is frequently associated with metabolic reprogramming in tumor cells. Our prior studies demonstrated that endothelial cell-specific molecule 1 (ESM1) promotes vascular mimicry (VM) formation and lactate production in OC cells. Here, we elucidated the molecular mechanism by which ESM1 drives VM formation and bevacizumab resistance through histone lactylation modifications, specifically H4K8 lactylation (H4K8la). Mechanistically, ESM1 facilitates H4K8la-mediated transcriptional activation of ERBB2, inducing heterodimerization between ERBB2 and EGFR to activate the downstream Akt/mTOR cascade. This cascade suppresses autophagy and activates STAT3 signaling, ultimately promoting VM formation. Pharmacological inhibition of lactylation or ERBB2 signaling effectively blocks VM formation and synergizes with bevacizumab in patient-derived preclinical models, significantly enhancing therapeutic efficacy. Our findings reveal ESM1 as a metabolic switch bridging transcriptional regulation and metabolic reprogramming via histone lactylation. The results of this study indicate that targeting ESM1 modulation could be a strategy to overcome bevacizumab resistance in OC.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12964-026-03071-z.",
  "abstract_shown": true,
  "affiliations": [
    "School of Basic Medical Sciences, Hunan Normal University, Changsha, Hunan 410000 China",
    "Department of Assisted Reproductive Centre, The Affiliated Zhuzhou Hospital of Xiangya Medical School, Central South University, Zhuzhou, Hunan 412007 China",
    "Tumor ImmunoMetabolism Institute (TIMI), The Affiliated Zhuzhou Hospital of Xiangya Medical School, Central South University, Zhuzhou, Hunan 412007 China",
    "Hunan Normal University Affiliated Xiangnan Hospital, 922 Hospital of PLA, Hunan Normal University, Hengyang, Hunan 410011 China",
    "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001 China",
    "Cancer Research Institute, Hunan Cancer Hospital, Hunan Normal University, Changsha, Hunan 410000 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yukun Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Juan Zou"
    },
    {
      "affs": [
        2
      ],
      "name": "Li Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiongjin Tan"
    },
    {
      "affs": [
        1
      ],
      "name": "Xing Tang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Peiting Wu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Xueru Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Xun Chen"
    },
    {
      "affs": [
        4
      ],
      "name": "Daichao Wu"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Xing Yu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ab2085f101geg.bib",
  "cited_by": 0,
  "doi": "10.1186/s12964-026-03071-z",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712071/",
  "id": "ab2085f101geg",
  "issns": [
    "1478-811X"
  ],
  "landing_url": "https://doi.org/10.1186/s12964-026-03071-z",
  "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",
      "Research"
    ],
    [
      "openalex",
      "1306|Cancer, Hypoxia, and Metabolism"
    ]
  ],
  "openalex": "W7171821429",
  "pdf_url": null,
  "pmcid": "PMC13712071",
  "pmid": "42947152",
  "published": "2026-07-30",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/ab2085f101geg.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:43Z",
      "native_id": "PMC13712071",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12964-026-03071-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Hypoxia, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "ESM1 drives H4K8 lactylation to promote vasculogenic mimicry and bevacizumab resistance in ovarian cancer",
  "title_text": "ESM1 drives H4K8 lactylation to promote vasculogenic mimicry and bevacizumab resistance in ovarian cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:43Z",
  "url": "https://research.draconitic.com/paper/ab2085f101geg",
  "venue": "Cell Communication and Signaling : CCS",
  "versions": []
}