{
  "abstract": "Esophageal squamous cell carcinoma (ESCC) lacks effective targeted therapies, and how metabolic reprogramming drives oncogenic signaling remains poorly defined. Here, we identify histone H3 lysine 23 lactylation (H3K23la) as a key epigenetic mediator linking lactate accumulation to tumor progression. H3K23la is upregulated in ESCC and correlates with poor prognosis. Mechanistically, H3K23la promotes WNK lysine deficient protein kinase 1 (WNK1) transcription, which increases histone H3 Ser10 phosphorylation (p‐H3S10) and enhances AKT transcription, thereby driving PI3K‐AKT signaling. This defines a lactate‐H3K23la‐WNK1‐p‐H3S10‐AKT axis connecting metabolism to oncogenic signaling. Importantly, pharmacological inhibition of WNK1 by CD03017 disrupts this pathway and suppresses tumor growth in vitro and in patient‐derived xenograft (PDX) models. In conclusion, our findings define a metabolic‐epigenetic‐signaling axis in ESCC and establish WNK1 as a potential therapeutic target downstream of histone lactylation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathophysiology School of Basic Medical Sciences Zhengzhou University Zhengzhou Henan China",
    "China‐US (Henan) Hormel Cancer Institute Zhengzhou Henan China",
    "Department of Radiology Zhengzhou University People's Hospital & Henan Provincial People's Hospital Zhengzhou China",
    "Henan Key Laboratory of Chronic Disease Management Fuwai Central China Cardiovascular Hospital Zhengzhou China",
    "Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou China",
    "Tianjian Laboratory of Advanced Biomedical Sciences Institute of Advanced Biomedical Sciences Zhengzhou University Zhengzhou Henan China",
    "State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer School of Basic Medical Sciences Zhengzhou University Zhengzhou Henan China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mingyang Yan"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Shaobo Fang",
      "orcid": "0000-0003-0645-5463"
    },
    {
      "affs": [
        1
      ],
      "name": "Yanming Song"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lei Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kexin Zhao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhenwei Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Yang Shao"
    },
    {
      "affs": [
        3
      ],
      "name": "Meng Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xinyang Jia"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qinxin Guo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mee‐Hyun Lee"
    },
    {
      "affs": [
        1,
        3,
        4,
        5,
        6
      ],
      "name": "Guoguo Jin"
    },
    {
      "affs": [
        0,
        1,
        5,
        6
      ],
      "name": "Zigang Dong",
      "orcid": "0000-0002-4174-4028"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1vz5d3hw41sgb.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78438",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696526/",
  "id": "1vz5d3hw41sgb",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.78438",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7223572015",
  "pdf_url": "https://europepmc.org/articles/PMC13696526?pdf=render",
  "pmcid": "PMC13696526",
  "pmid": "42928409",
  "published": "2026-10-25",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/1vz5d3hw41sgb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:52Z",
      "native_id": "PMC13696526",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78438"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928409",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928409"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Epigenetics and DNA Methylation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Histone Lactylation Drives WNK1 Expression to Promote Esophageal Squamous Cell Carcinoma Progression Through Histone H3 Ser10 Phosphorylation",
  "title_text": "Histone Lactylation Drives WNK1 Expression to Promote Esophageal Squamous Cell Carcinoma Progression Through Histone H3 Ser10 Phosphorylation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:51Z",
  "url": "https://research.draconitic.com/paper/1vz5d3hw41sgb",
  "venue": "Advanced Science",
  "versions": []
}