Multi-omics and Functional Analyses Identify Cancer-associated Fibroblast-derived Insulin-like Growth Factor 1 as a Stromal Mediator of Lung Adenocarcinoma Progression.
5 affiliations
- 1Department of Medical Oncology School of Medicine Sir Run Run Shaw Hospital Zhejiang University Hangzhou China.
- 2Department of Pathology and International Institutes of Medicine The Fourth Affiliated Hospital (Yiwu) Zhejiang University School of Medicine Hangzhou China.
- 3Department of Pathology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
- 4Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China.
- 5Department of Medical Oncology Zhejiang Cancer Hospital Hangzhou China.
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.
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BibTeX
@article{deng2026multiomics,
title = {{Multi-omics and Functional Analyses Identify Cancer-associated Fibroblast-derived Insulin-like Growth Factor 1 as a Stromal Mediator of Lung Adenocarcinoma Progression.}},
author = {Jingwen Deng and Jin Sheng and Liangkun You and Qizhen Han and Yueyang Wang and Hong Pan and Yadong Lu and Xiaopeng Cai and Hao Liu and Weidong Han},
journal = {MedComm},
year = {2026},
month = nov,
doi = {10.1002/mco2.71123},
url = {https://europepmc.org/article/MED/42996906},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-omics and Functional Analyses Identify Cancer-associated Fibroblast-derived Insulin-like Growth Factor 1 as a Stromal Mediator of Lung Adenocarcinoma Progression.
AU - Jingwen Deng
AU - Jin Sheng
AU - Liangkun You
AU - Qizhen Han
AU - Yueyang Wang
AU - Hong Pan
AU - Yadong Lu
AU - Xiaopeng Cai
AU - Hao Liu
AU - Weidong Han
PY - 2026
DA - 2026/11/05
JO - MedComm
DO - 10.1002/mco2.71123
UR - https://europepmc.org/article/MED/42996906
AB - 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.
SN - 2688-2663
ER -