{
  "abstract": "Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, yet the stromal mechanisms driving rapid disease progression are incompletely understood. Here, we integrated single-cell RNA sequencing with exploratory whole-exome sequencing to characterize tumor microenvironment remodeling in a rapidly progressing LUAD patient. Tumor tissue exhibited marked stromal enrichment, with inflammatory cancer-associated fibroblasts (CAFs) constituting a prominent fibroblast subset. Receptor-ligand and cell-type-specific expression analyses identified CAF-derived insulin-like growth factor 1 (IGF1) as a potential stromal mediator of LUAD progression. This fibroblast-specific IGF1 pattern was corroborated by an external single-cell dataset and by immunofluorescence validation in LUAD tissues with or without bone metastasis. Functionally, recombinant IGF1 enhanced LUAD cell proliferation, migration, and invasion, whereas IGF1 knockdown in CAF-like cells attenuated these malignant phenotypes in co-culture models. In vivo, IGF1 knockdown in CAF-like cells reduced distant metastatic burden, accompanied by alterations in Wnt-related signaling, extracellular matrix organization, and metastasis-associated molecules. These findings indicate that CAF-derived IGF1 contributes to LUAD progression and bone metastatic remodeling through paracrine stromal-tumor communication, highlighting the IGF1/IGF1R axis as a potential stromal-directed therapeutic target in selected LUAD patients.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Oncology School of Medicine Sir Run Run Shaw Hospital Zhejiang University Hangzhou China.",
    "Department of Pathology and International Institutes of Medicine The Fourth Affiliated Hospital (Yiwu) Zhejiang University School of Medicine Hangzhou China.",
    "Department of Pathology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.",
    "Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China.",
    "Department of Medical Oncology Zhejiang Cancer Hospital Hangzhou China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jingwen Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Jin Sheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Liangkun You"
    },
    {
      "affs": [
        1
      ],
      "name": "Qizhen Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Yueyang Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hong Pan"
    },
    {
      "affs": [
        1
      ],
      "name": "Yadong Lu"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiaopeng Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Hao Liu"
    },
    {
      "affs": [
        4
      ],
      "name": "Weidong Han",
      "orcid": "0000-0001-7227-3671"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9as64svs4q1pa.bib",
  "cited_by": 0,
  "doi": "10.1002/mco2.71123",
  "fulltext_url": "https://europepmc.org/articles/PMC13740674",
  "id": "9as64svs4q1pa",
  "issns": [
    "2688-2663"
  ],
  "landing_url": "https://europepmc.org/article/MED/42996906",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Cells and Metastasis"
    ]
  ],
  "openalex": "W7225428034",
  "pdf_url": "https://europepmc.org/articles/PMC13740674?pdf=render",
  "pmcid": "PMC13740674",
  "pmid": "42996906",
  "published": "2026-11-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9as64svs4q1pa.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "MED:42996906",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42996906"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Cells and Metastasis",
      "subfield": "oncology"
    }
  ],
  "title": "Multi-omics and Functional Analyses Identify Cancer-associated Fibroblast-derived Insulin-like Growth Factor 1 as a Stromal Mediator of Lung Adenocarcinoma Progression.",
  "title_text": "Multi-omics and Functional Analyses Identify Cancer-associated Fibroblast-derived Insulin-like Growth Factor 1 as a Stromal Mediator of Lung Adenocarcinoma Progression.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/9as64svs4q1pa",
  "venue": "MedComm",
  "versions": []
}