{
  "abstract": "Hyperglycemia is an independent risk factor for poor prognosis in non-small cell lung cancer (NSCLC), yet the underlying metabolic-oncogenic crosstalk remains incompletely defined. The hexosamine biosynthetic pathway (HBP) senses glucose flux and generates UDP-GlcNAc for O-GlcNAcylation, a post-translational modification catalyzed by O-GlcNAc transferase (OGT). Here we investigate whether and how high glucose exploits OGT-mediated O-GlcNAcylation to fuel NSCLC malignancy. A549 and H1299 NSCLC cells were cultured in normal (5.5 mM) or high (25 mM) glucose. Proliferation, colony formation, migration, invasion, wound healing, and apoptosis were evaluated. OGT and global O-GlcNAc levels were assessed in tumor versus adjacent normal tissues by immunohistochemistry and in cells by western blotting. Stable OGT-knockdown (sh-OGT) lines were generated to dissect functional requirements. PI3K/AKT/mTOR pathway activation was examined by phospho-specific western blotting. The cell lines were tested and confirmed to be mycoplasma-free. High glucose significantly enhanced proliferation, clonogenicity, migration, and invasion, and suppressed apoptosis by downregulating Bax and upregulating Bcl-2. OGT and global O-GlcNAcylation were markedly upregulated in NSCLC tissues and in high-glucose-treated cells. OGT silencing abrogated high-glucose-induced malignant phenotypes, restored apoptotic sensitivity, and reverted the Bax/Bcl-2 ratio. Mechanistically, high-glucose-driven O-GlcNAcylation activated PI3K, AKT, and mTOR phosphorylation, whereas OGT knockdown blunted this activation. OGT-orchestrated hyper-O-GlcNAcylation is a pivotal conduit linking the hyperglycemic microenvironment to PI3K/AKT/mTOR-dependent NSCLC progression. Targeting OGT-mediated O-GlcNAcylation may offer a precision therapeutic strategy for NSCLC patients with comorbid diabetes or hyperglycemia.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.",
    "Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Guo-Dong Shi"
    },
    {
      "affs": [
        1
      ],
      "name": "Hui-Jiang Gao"
    },
    {
      "affs": [
        1
      ],
      "name": "Dong Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yu-Cheng Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Peng Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dqbhfkz701d8t.bib",
  "cited_by": 0,
  "doi": "10.21037/tcr-2026-2076",
  "fulltext_url": "https://europepmc.org/articles/PMC13743261",
  "id": "dqbhfkz701d8t",
  "issns": [
    "2218-676X",
    "2219-6803"
  ],
  "landing_url": "https://europepmc.org/article/MED/42997903",
  "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": [
    [
      "openalex",
      "1312|Glycosylation and Glycoproteins Research"
    ]
  ],
  "openalex": "W7224134017",
  "pdf_url": "https://europepmc.org/articles/PMC13743261?pdf=render",
  "pmcid": "PMC13743261",
  "pmid": "42997903",
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dqbhfkz701d8t.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42997903",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42997903"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Glycosylation and Glycoproteins Research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "High glucose drives non-small cell lung cancer progression via OGT-mediated O-GlcNAcylation and PI3K/AKT/mTOR pathway activation.",
  "title_text": "High glucose drives non-small cell lung cancer progression via OGT-mediated O-GlcNAcylation and PI3K/AKT/mTOR pathway activation.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/dqbhfkz701d8t",
  "venue": "Translational cancer research",
  "versions": []
}