{
  "abstract": "ATP citrate lyase (ACLY) is a pivotal enzyme implicated in cancer cells’ aberrant survival and proliferation. However, its precise role in tumor endothelial cells (TECs) in tumor angiogenesis and malignant progression remains poorly defined. Our previous studies have identified a high distribution of ginsenoside Rd in TECs, yet the mechanism underlying its anti-angiogenic properties has not been elucidated. Here, we clarify the direct regulatory effects of ACLY in TECs and explain how Rd reprograms the ACLY metabolic pathway in TECs. Systemic Acly silencing in tumor models resulted in suppressed angiogenesis and tumor progression. Importantly, TEC-specific Acly knockdown directly disrupted pathological vascularization and exerted comparable inhibitory effects on tumor growth. Metabolomic profiling revealed that ginsenoside Rd reduced nuclear acetyl-coenzyme A (acetyl-CoA) levels by down-regulating ACLY expression, thereby inhibiting the transcription of angiogenesis-related factors through reduced acetylation of histone H3 (but not H4). Mechanistically, ginsenoside Rd promotes the ubiquitin-mediated degradation of ACLY by targeting and suppressing ubiquitin-specific peptidase 13 (USP13). This study not only establishes a mechanistic framework for the development of ACLY-centric therapeutic strategies to reprogram pathological vasculature but also identifies the natural compound Rd as a pharmacological modulator of TECs metabolism via targeting the USP13–ACLY axis.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China",
    "School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China",
    "Department of Digestive Tumor Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China",
    "Department of Colorectal Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Haobin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Haocheng Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiali Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Qixiang Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lingge Cheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Li Wan"
    },
    {
      "affs": [
        1
      ],
      "name": "Mengyuan Gao"
    },
    {
      "affs": [
        2
      ],
      "name": "Yujie Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Xinping Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xue Zhou"
    },
    {
      "affs": [
        1
      ],
      "name": "Sainan Peng"
    },
    {
      "affs": [
        3
      ],
      "name": "Lihua Shao"
    },
    {
      "affs": [
        0
      ],
      "name": "Guangji Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Chao Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Chongjin Zhong"
    },
    {
      "affs": [
        0
      ],
      "name": "Fang Zhou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5a6tmy3rtjc7g.bib",
  "cited_by": 0,
  "doi": "10.1016/j.apsb.2026.09.002",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13729718/?tool=EBI",
  "id": "5a6tmy3rtjc7g",
  "issns": [
    "2211-3835",
    "2211-3843"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13729718",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "3004|Ginseng Biological Effects and Applications"
    ]
  ],
  "openalex": "W7208827830",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13729718/pdf/?tool=EBI",
  "pmcid": "PMC13729718",
  "pmid": "42979447",
  "published": "2026-09-05",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/5a6tmy3rtjc7g.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "PMC:PMC13729718",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13729718"
    },
    {
      "first_seen": "2026-11-07T12:22:28Z",
      "native_id": "PMC13729718",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.apsb.2026.09.002"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3004|Ginseng Biological Effects and Applications",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Targeting the USP13–ACLY axis in tumor endothelial cells: Ginsenoside Rd suppresses pathological angiogenesis through metabolic-epigenetic reprogramming",
  "title_text": "Targeting the USP13–ACLY axis in tumor endothelial cells: Ginsenoside Rd suppresses pathological angiogenesis through metabolic-epigenetic reprogramming",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:28Z",
  "url": "https://research.draconitic.com/paper/5a6tmy3rtjc7g",
  "venue": "Acta pharmaceutica Sinica. B",
  "versions": []
}