{
  "abstract": "Hypoxia-driven epigenetic remodeling is a critical determinant of lung adenocarcinoma (LUAD) progression and therapeutic resistance, yet the epigenetic mechanisms coordinating hypoxia signaling with tumor microenvironment remodeling remain incompletely understood. Here, by integrating LUAD cell models, murine tumor models, and spatial transcriptomics with reference-based cell-type deconvolution, we identify SATB2 as a previously unrecognized hypoxia-inducible epigenetic regulator in LUAD. HIF-1α, unlike HIF-2α, directly interacts with the promoter of SATB2, promoting its expression in hypoxic environments. Increased levels of SATB2 have been linked to more severe clinical and pathological characteristics as well as poorer outcomes for patients. Mechanistically, SATB2 physically interacts with HIF-1α and p300, while SATB2 loss reduces H3K27 acetylation and elongating RNA polymerase II occupancy at HIF-1 target loci, supporting a model in which SATB2 facilitates HIF-1α-dependent transcriptional elongation and establishes a positive feedback circuit that amplifies hypoxia-responsive transcriptional programs. Spatial transcriptomic analyses further show that SATB2-associated hypoxic programs are preferentially enriched within malignant tumor niches and are associated with remodeling of the local tumor microenvironment. Functionally, SATB2 promotes LUAD growth, metastasis, angiogenesis, and bevacizumab resistance in a HIF-1α-dependent manner, whereas genetic disruption of SATB2 or pharmacological inhibition of p300 enhances sensitivity to anti-angiogenic therapy. Collectively, these findings identify the SATB2-p300-HIF-1α axis as a hypoxia-responsive epigenetic regulatory mechanism linking transcriptional adaptation to malignant progression and resistance to anti-angiogenic therapy, and provide a preclinical rationale for further investigation of this pathway as a potential therapeutic vulnerability in LUAD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Jiangsu, Suzhou, 215006, China; Department of Medical Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Jiangsu, Suzhou, 215000, China.",
    "Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Jiangsu, Suzhou, 215000, China.",
    "Research Center for Experimental Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin Road II, Shanghai, 200025, China.",
    "Department of Medical Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Jiangsu, Suzhou, 215000, China.",
    "Department of Medical Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Jiangsu, Suzhou, 215000, China. Electronic address: guofeng27@njmu.edu.cn.",
    "Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Jiangsu, Suzhou, 215006, China. Electronic address: cky9920@163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Suhong Ruan"
    },
    {
      "affs": [
        1
      ],
      "name": "Tengteng Wei"
    },
    {
      "affs": [
        1
      ],
      "name": "Guangda Yuan"
    },
    {
      "affs": [
        2
      ],
      "name": "Yan Shen"
    },
    {
      "affs": [
        3
      ],
      "name": "Yangzi Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Jing Ning"
    },
    {
      "affs": [
        4
      ],
      "name": "Feng Guo"
    },
    {
      "affs": [
        5
      ],
      "name": "Kai Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/becfz17fayf71.bib",
  "cited_by": 0,
  "doi": "10.1016/j.tranon.2026.103069",
  "fulltext_url": "https://europepmc.org/articles/PMC13691162",
  "id": "becfz17fayf71",
  "issns": [
    "1936-5233"
  ],
  "landing_url": "https://europepmc.org/article/MED/42896440",
  "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",
      "1306|Cancer, Hypoxia, and Metabolism"
    ]
  ],
  "openalex": "W7222928078",
  "pdf_url": "https://europepmc.org/articles/PMC13691162?pdf=render",
  "pmcid": "PMC13691162",
  "pmid": "42896440",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/becfz17fayf71.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42896440",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42896440"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Hypoxia, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "Hypoxia-induced SATB homeobox 2 increases hypoxia-inducible factor-1-dependent tumorigenesis and drives bevacizumab resistance in lung adenocarcinoma.",
  "title_text": "Hypoxia-induced SATB homeobox 2 increases hypoxia-inducible factor-1-dependent tumorigenesis and drives bevacizumab resistance in lung adenocarcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/becfz17fayf71",
  "venue": "Translational oncology",
  "versions": []
}